Language：English   Publishing type：Research paper (scientific journal)  

Our previous studies demonstrated that prenatal bisphenol A (BPA) exposure affected the hepatic transcriptome and lipidome in rat offspring in a sex- and age-dependent manner. In this study, we investigated the effects of gestational exposure to BPA on the rat dams, after weaning period, and compared them with those of their offspring. Our results showed alterations in hepatic transcriptome related to insulin signaling, circadian rhythm, and infectious disease pathways in BPA-treated dams even 4 weeks after the exposure, whereas slight modifications on the lipid profile were found. Alterations in lipid and transcriptome profiles were more prominent in the prenatally BPA-exposed offspring at postnatal day (PND) 1 and 21 than those in the dams, suggesting that in utero exposure to BPA is more serious than exposure in the adulthood. Cryptochrome-1 (Cry1) and peroxisome proliferator-activated receptor delta (Ppard) were commonly altered in both dams and offspring. Nevertheless, the results of DIABLO (Data Integration Analysis for Biomarker discovery using Latent cOmponents), showed that multi-omics data successfully distinguished the exposed dams from the corresponding controls and their offspring with a high level of accuracy. The accuracy rates in BPA50 models (including control and 50 μg BPA/kg bw/day exposed groups) were smaller than those in BPA5000 models (control and 5000 μg BPA/kg bw/day exposed groups), suggesting dose-dependent severity in BPA effects. Palmitic acid and genes related to circadian rhythm, insulin responses, and lipid metabolism (e.g., 1-acylglycerol-3-phosphate O-acyltransferase 2 (Agpat2), B-cell CLL/lymphoma 10 (Bcl10), Cry1, Harvey rat sarcoma virus oncogene (Hras), and NLR family member X1 (Nlrx1)) were identified through DIABLO models as novel biomarkers of effects of BPA across two generations.

DOI： 10.1016/j.scitotenv.2022.153990

PubMed

researchmap

Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.cbpc.2022.109325

researchmap

Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.ecoenv.2022.113538

researchmap

Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.scitotenv.2021.150631

researchmap

Publishing type：Research paper (scientific journal)   Publisher：American Chemical Society (ACS)  

DOI： 10.1021/acs.est.1c01074

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.ecoenv.2021.111947

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

Neonicotinoid insecticides are used for agricultural and non-agricultural purposes worldwide. Pets are directly exposed to neonicotinoids in veterinary products and through environmental contamination. Cytochrome P450 (CYP) is among the most significant xenobiotic metabolizing enzymes that oxidizes several chemicals, including neonicotinoids. However, CYP activities and metabolite compositions of neonicotinoid metabolites are unknown in most domesticated pet species. Our objectives were to reveal the differences in metabolites of neonicotinoids (imidacloprid, clothianidin, and acetamiprid) and CYP activities among common pet species (cats and dogs), humans, and rats. The results indicated that the CYP-mediated neonicotinoid metabolism was different depending on species and each neonicotinoid. Among these four species, the kinetics of imidacloprid metabolism indicated that rats have the highest rate of oxidation of imidacloprid to 4OH-imidacloprid, while the greatest enzyme kinetics of imidacloprid metabolism to 5OH-imidacloprid were found in rats and humans. Clothianidin was rapidly metabolized to 1-methyl-3-nitroguanidine and dm-clothianidin in rats, but cats and humans showed the lowest formation of dm-clothianidin. CYP activities in metabolism of acetamiprid to dm-acetamiprid and N-acetyl-acetamiprid were determined to be significantly higher in humans compared to other species. However, further studies should be targeted at identifying the differences in hepatic metabolism of neonicotinoids in these species using recombinant CYP enzymes.

DOI： 10.1016/j.cbpc.2020.108898

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

Tris(2-chloroethyl) phosphate (TCEP) is an organophosphate flame retardant that used in textiles, industrial materials, and furniture to delay the spread of fire after ignition. TCEP has been detected in the tissues and eggs of fish and birds. However, there are no studies regarding the effects of TCEP on avian embryos. In the present study, we investigated the developmental toxicity of TCEP exposure on chicken embryos in a shell-less incubation system, which enables in situ observation. Chicken embryos were treated with graded doses of TCEP (50, 250, and 500 nmol/g egg) on incubation day 0. The survival rate, morphological biometrics, heart rate, and length and branch number of extraembryonic blood vessels were measured on incubation days 3-9. Survival rates were reduced from incubation day 3 and were significantly decreased until day 9. Body length, head + bill length and eye diameter were significantly reduced by TCEP exposure. Regarding skeletal effects, spine length was decreased in a dose-dependent manner on day 9. Body weight on day 9 significantly reduced in all TCEP treatment groups. These results suggest that TCEP exposure to >50 nmol/g egg retards development in chicken embryos. TCEP exposure to 500 nmol/g egg significantly increased heart weight to body weight ratio in the embryos. More than 250 nmol/g egg of TCEP significantly reduced the heart rate of embryos in the early developmental stage. The formation of extraembryonic blood vessels and the number of erythrocytes were significantly reduced even with 50 nmol/g egg of TCEP. These findings suggest that TCEP exposure specifically affects the cardiovascular system in chicken embryos, which leads to developmental delay. The results of this study also demonstrate that the shell-less incubation system can be used to continuously monitor the effects of chemicals on developing avian embryos.

DOI： 10.1016/j.ecoenv.2020.111263

PubMed

researchmap

Publishing type：Research paper (scientific journal)   Publisher：American Chemical Society (ACS)  

DOI： 10.1021/acs.est.0c04763

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

Bisphenol A (BPA) is a well-known endocrine disruptor that has obesogenic properties. We have previously reported sex- and age-dependent changes in hepatic transcriptome and proteome of several lipid homeostasis-related genes in rat offspring prenatally exposed to BPA. To further understand the impacts of prenatal BPA exposure, we analyzed lipidomic profiles in the postnatal day (PND) 21 and 60 rats using a high-resolution QTOF mass spectrometer coupled with a HPLC system. We found that the total lipid content was significantly decreased in PND21 females prenatally exposed to 5000 μg/kg bw/day of BPA. Levels of total fatty acids, acylcarnitines, and monoacylglycerols significantly increased in both female and male BPA-exposed rats at PND21. An elevation in total cholesterol esters and reductions in triacylglycerols and monogalactosyl diacylglycerols were found only in PND21 females prenatally exposed to BPA. Interestingly, opposite responses were observed for phospholipids and sphingolipids between PND21 females and males following BPA exposure. The effects on the body weight and total lipid content were mitigated in the latter stage, although the alterations of lipid profiles continued until PND60. A Data Integration Analysis for Biomarker discovery using Latent cOmponents (DIABLO) revealed a high correlation of the lipidome with our previously published transcriptome data. DIABLO also identified potential biomarkers of prenatal exposure to BPA; glycerol-3-phosphate dehydrogenase 1 (Gpd1) and glyceronephosphate O-acyltransferase (Gnpat), which are involved in the glycerophospholipid metabolism, in females and males, respectively. Collectively, we highlighted the sex- and age-dependent effects of prenatal BPA exposure on hepatic lipid homeostasis in rat offspring.

DOI： 10.1016/j.scitotenv.2020.143466

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：American Chemical Society (ACS)  

Prenatal hydroxylated polychlorinated biphenyls (OH-PCBs) exposure may disrupt fetal brain development during the critical period of thyroid hormone (TH) action. However, there are limited studies on the OH-PCB transfer to the fetal brain, particularly in primates. In this study, we selected the Japanese macaque (Macaca fuscata) as a model animal for the fetal transfer of OH-PCBs in humans and revealed OH-PCB concentrations and their relationships in maternal and fetal blood, liver, and brain. l-thyroxine (T4)-like OH-PCBs including 4OH-CB187, a major congener in humans, were found in high proportions in the blood, liver, brain, and placenta of pregnant Japanese macaques. OH-PCBs were detected in the fetal brain and liver in the first trimester, indicating their transfer to the brain in the early pregnancy stage. 4OH-CB187 and 4OH-CB202 were the major congeners found in fetal brain, indicating that these T4-like OH-PCBs are transported from maternal blood to the fetal brain via the placenta. These results indicate that further studies are needed on the effects of OH-PCBs on the developing fetal brain.

DOI： 10.1021/acs.est.0c01805

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.envpol.2020.114642

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.ecoenv.2020.110835

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Frontiers Media SA  

Marine aquaculture fish and the environment are possible hot spots for the maintenance and spread of antibiotic resistance genes (ARGs). We here show the time courses of changes of six tetracycline resistance genes (tet) in fish rearing seawater and fish intestine in tank experiments. Experimental tanks were prepared as oxytetracycline (OTC) administration tanks and those without OTC. It was found that tet(B), tet(M), and tet(W) were dominant in seawater among the six tet genes. tet(B) and tet(M) abundances increased immediately after OTC administration, indicating that OTC served as a selective pressure to increase the proportion of tet-possessing bacteria. In contrast, the abundance of tet genes in the fish intestine did not differ between the with- and without-OTC administration groups, and clearly was not altered by OTC administration. Profile changing of tet in seawater and fish intestine did not synchronize. These observations suggested that the dynamics of intestinal tet-possessing bacteria do not directly reflect the environment, but reflect selection within the intestine.

DOI： 10.3389/fmicb.2020.01764

PubMed

researchmap

Publishing type：Research paper (scientific journal)   Publisher：American Chemical Society (ACS)  

DOI： 10.1021/acs.est.9b07471

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

Developmental exposure to bisphenol A (BPA) is associated with liver dysfunction and diseases in adulthood. The aims of this study were to assess the effects of prenatal BPA exposure on the hepatic transcriptome and proteome in female and male offspring and to understand adverse outcome pathways (AOPs) to observed phenotypic effects. Pregnant Wistar rats were exposed to 50 or 5000 μg BPA/kg bw/day, or 17β-estradiol (E2, 50 μg/kg bw/day) from embryonic day 3 to 18. The liver transcriptome and proteome profiles were analyzed in the newborn (postnatal day 1; PND1) and weaning (PND21) rat offspring. Based on the differentially expressed genes/proteins derived from transcriptome and proteome profiles, we performed pathway, transcription factor, and disease enrichment analyses. A principal component analysis of transcriptome data demonstrated that prenatal BPA exposure caused masculinization of the hepatic transcriptome in females. Both of transcriptomic and proteomic data showed that prenatal BPA exposure led to the disruption of cell cycle, lipid homeostasis, and hormone balance in offspring. Most of the effects at the transcript level were extended from newborn to weaning in males, but were moderated until weaning in females. The alterations at the transcript and protein levels were accordant with the observation of increases in body weight and anogenital distance and changes in hepatosomatic index in the offspring. Collectively, we constructed AOPs with evidence of sex- and age-specific actions of prenatal BPA exposure in the offspring.

DOI： 10.1016/j.scitotenv.2020.137568

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：American Chemical Society (ACS)  

DOI： 10.1021/acs.est.9b05941

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Polychlorinated biphenyls (PCBs) and their hydroxylated metabolites (OH-PCBs) might disrupt thyroid function. However, there is no clear evidence of PCB exposure disrupting thyroid hormone (TH) homeostasis in dogs and cats. The present study conducted in vivo experiments to evaluate the effects of a mixture of 12 PCB congeners (CB18, 28, 70, 77, 99, 101, 118, 138, 153, 180, 187 and 202, each congener 0.5 mg/kg BW, i.p. administration) on serum TH levels in male dogs (Canis lupus familiaris) and male cats (Felis silvestris catus). In PCB-exposed dogs, the time courses of higher-chlorinated PCBs and L-thyroxine (T4)-like OH-PCBs (4-OH-CB107 and 4-OH-CB202) concentrations were unchanged or tended to increase, whereas those of lower-chlorinated PCBs and OH-PCBs tended to decrease after 24 h. In PCB-exposed cats, concentrations of PCBs increased until 6 h and then remained unchanged. The levels of lower-chlorinated OH-PCBs including 4'-OH-CB18 increased until 96 h and then decreased. In PCB-exposed dogs, free T4 concentrations were higher than those in the control group at 48 and 96 h after PCB administration and positively correlated with the levels of T4-like OH-PCBs, suggesting competitive binding of T4 and T4-like OH-PCBs to a TH transporter, transthyretin. Serum levels of total T4 and total 3,3',5-triiodo-L-thyronine (T3) in PCB-exposed dogs were lower than in the control group at 24 and 48 h and negatively correlated with PCB concentrations, implying that PCB exposure enhanced TH excretion by increasing TH uptake and TH conjugation enzyme activities in the dog liver. In contrast, no obvious changes in TH levels were observed in PCB-exposed cats. This could be explained by the lower levels of T4-like OH-PCBs and lower hepatic conjugation enzyme activities in cats compared with dogs. Different effects on serum TH levels in PCB-exposed dogs and cats are likely to be attributable to species-specific PCB and TH metabolism.

DOI： 10.1016/j.scitotenv.2019.06.300

PubMed

researchmap

DOI： 10.1016/j.ecoenv.2019.06.033

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Canis lupus familiaris (domestic dog) possess a high capacity to metabolize higher-chlorinated polychlorinated biphenyls (PCBs) to thyroid hormone (TH)-like hydroxylated PCB metabolites (OH-PCBs). As a result, the brain could be at high risk of toxicity caused by OH-PCBs. To evaluate the effect of OH-PCBs on dog brain, we analyzed OH-PCB levels in the brain and the metabolome of the frontal cortex following exposure to a mixture of PCBs (CB18, 28, 70, 77, 99, 101, 118, 138, 153, 180, 187, and 202). 4-OH-CB202 and 4-OH-CB107 were major OH-PCBs in the brain of PCB-exposed dogs. These OH-PCBs were associated with metabolites involved in urea cycle, proline-related compounds, and purine, pyrimidine, glutathione, and amino-acid metabolism in dog brain. Moreover, adenosine triphosphate levels in the PCBs exposure group were significantly lower than in the control group. These results suggest that OH-PCB exposure is associated with a disruption in TH homeostasis, generation of reactive oxygen species, and/or disruption of oxidative phosphorylation (OXPHOS) in brain cells. Among them, OXPHOS disturbance could be associated with both disruptions in cellular amino-acid metabolism and urea cycle. Therefore, an OXPHOS activity assay was performed to evaluate the disruption of OXPHOS by OH-PCBs. The results indicated that 4-OH-CB107 inhibits the function of Complexes III, IV, and V of the electron transport chain, suggesting that 4-OH-CB107 inhibit these complexes in OXPHOS. The neurotoxic effects of PCB exposure may be mediated through mitochondrial toxicity of OH-PCBs in the brain.

DOI： 10.1016/j.taap.2019.114620

PubMed

researchmap

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

DOI： 10.1002/ieam.4137

researchmap

Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/ieam.4137

researchmap

Publishing type：Research paper (scientific journal)  

© 2019 American Chemical Society. In this study, we assessed the binding affinities of perfluoroalkyl substances (PFASs), including perfluoroalkyl carboxylates (PFCAs) and perfluoroalkyl sulfonates (PFSAs), to the ligand-binding domains (LBDs) of Baikal seal (Pusa sibirica; bs) and human (h) peroxisome proliferator-activated receptor alpha (PPARα). An in vitro competitive binding assay showed that six PFCAs and two PFSAs could bind to recombinant bs and hPPARα LBD proteins in a dose-dependent manner. The relative binding affinities (RBAs) of PFASs to bsPPARα were as follows: PFOS > PFDA > PFNA > PFUnDA > PFOA > PFHxS > PFHpA > PFHxA. The RBAs to bsPPARα showed a significant positive correlation with those to hPPARα. In silico PPARα homology modeling predicted that there were two ligand-binding pockets (LBPs) in the bsPPARα and hPPARα LBDs. Structure-activity relationship analyses suggested that the binding potencies of PFASs to PPARα might depend on LBP binding cavity volume, hydrogen bond interactions, the number of perfluorinated carbons, and the hydrophobicity of PFASs. Interspecies comparison of the in vitro binding affinities revealed that bsPPARα had higher preference for PFASs with long carbon chains than hPPARα. The in silico docking simulations suggested that the first LBP of bsPPARα had higher affinities than that of hPPARα however, the second LBP of bsPPARα had lower affinities than that of hPPARα. To our knowledge, this is the first evidence showing interspecies differences in the binding of PFASs to PPARαs and their structure-activity relationships.

DOI： 10.1021/acs.est.8b07273

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.ecoenv.2018.09.043

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.envpol.2018.06.071

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

© 2018 American Chemical Society. We investigated the Baikal seal (Pusa sibirica) peroxisome proliferator-activated receptor α (bsPPARα) transactivation potencies of polybrominated diphenyl ethers (PBDEs) using an in vitro bsPPARα reporter gene assay. BDE47, BDE99, and BDE153 induced bsPPARα-mediated transcriptional activities in a dose-dependent manner. To compare bsPPARα transactivation potencies of PBDEs, perfluorooctanoic acid (PFOA)-based relative potencies (REPs), a ratio of 50% effective concentration of PFOA to the test chemical, were determined. The order of REPs of PBDEs was BDE153 (13) > BDE99 (8.1) > BDE47 (6.6) > PFOA (1.0) > BDE100, BDE154, and BDE183 (not activated). PBDEs with two bromine atoms at the ortho position showed higher bsPPARα transactivation potencies than those with three bromine atoms. Comparison of the lowest-observed-effect concentration in bsPPARα reporter gene assays revealed that BDE99 was 7-fold more potent than CB99, a polychlorinated biphenyl congener with the same IUPAC number, indicating that brominated congeners could more efficiently activate bsPPARα than chlorinated congeners. The REPs of PBDEs for bsPPARα transactivation were approximately 7- to 13-fold higher than those of perfluorochemicals (PFCs), suggesting that the effects of PBDEs on the bsPPARα signaling pathway may be superior to those of PFCs. This study provides the first evidence that PBDE congeners activate PPARα in vitro.

DOI： 10.1021/acs.est.8b02501

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Academic Press  

This work aimed at evaluating the toxic effects of in ovo exposure to phenobarbital (PB) and unveiling the mode of action by transcriptome analysis in the embryonic liver of a model avian species, chicken (Gallus gallus). Embryos were initially treated with saline or 1 μg PB /g egg at Hamburger Hamilton Stage (HHS) 1 (1st day), followed by 20 days of incubation to HHS 46. At 21st day, chicks that pipped successfully were euthanized and dissected for assessing the PB caused effects on phenotypes and the liver transcriptome in both genders. In the PB treatment group, a 7% attenuation in tarsus length was found in females. While no adverse phenotypic effect on the liver somatic index (LSI) was observed, PB caused significant changes in the expressions of 52 genes in males and 516 genes in females (False Discovery Rate &lt
0.2, p value &lt
0.05, and absolute fold change &gt
2). PB exposure modulated the genes primarily enriched in the biological pathways of the cancer, cardiac development, immune response, lipid metabolism, and skeletal development in both genders, and altered expressions of genes related to the cellular process and neural development in females. However, mRNA expressions of chicken xenobiotic receptor (CXR)-mediated CYP genes were not induced in the PB treatment groups, regardless of males and females. On the contrary, PB exposure repressed the mRNA expressions of CYP2AC2 in males and CYP2R1, CYP3A37, and CYP8B1 in females. Although transcription factors (TFs) including SREBF1 and COUP-TFII were predicted to be commonly activated in both genders, some TFs were activated in a gender-dependent manner, such as PPARa in males and BRCA1 and IRF9 in females. Taken together, our results provided an insight into the mode of action of PB on the chicken embryos.

DOI： 10.1016/j.ecoenv.2018.05.033

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Polychlorinated biphenyls (PCBs) and their hydroxylated metabolites (OH-PCBs) have been detected in tissues of both wild animals and humans. Several previous studies have suggested adverse effects of OH-PCBs on the endocrine and nervous systems in mammals. However, there have been no studies on transcriptome analysis of the effects of OH-PCBs, and thus, the whole picture and mechanisms underlying the adverse effects induced by OH-PCBs are still poorly understood. We therefore investigated the mRNA expression profile in the liver of adult male Wistar rats treated with 4-hydroxy-2,3,3',4',5-pentachlorobiphenyl (4-OH-CB107) to explore the genes responsive to OH-PCBs and to understand the potential effects of the chemical. Next-generation RNA sequencing analysis revealed changes in the expression of genes involved in the circadian rhythm and fatty acid metabolism, such as nuclear receptor subfamily 1, group D, member 1, aryl hydrocarbon receptor nuclear translocator-like protein 1, cryptochrome circadian clock 1, and enoyl-CoA hydratase and 3-hydroxyacyl-CoA dehydrogenase, in 4-OH-CB107-treated rats. In addition, biochemical analysis of the plasma revealed a dose-dependent increase in the leucine aminopeptidase, indicating the onset of liver damage. These results suggest that OH-PCB exposure may induce liver injury as well as disrupt the circadian rhythm and peroxisome proliferator-activated receptor-related fatty acid metabolism.

DOI： 10.1093/toxsci/kfy123

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Verlag  

In what has become known as the Yusho incident, thousands of people in western Japan were poisoned by the accidental ingestion of rice bran oil contaminated with polychlorinated biphenyls (PCBs) and various dioxins and dioxin-like compounds. In this study, we investigated the accumulation patterns of 69 PCB congeners in the blood of Yusho patients in comparison with those of non-exposed controls. The blood samples were collected at medical check-ups in 2004 and 2005. To compare the patterns of PCB congeners, we calculated the concentration ratio of each congener relative to the 2,2′,4,4′,5,5′-hexaCB (CB153) concentration. The concentration ratios of tetra- and penta-chlorinated congeners in the blood of Yusho patients were significantly lower than those of controls. To examine the cytochrome P450 (CYP)-dependent metabolic potential of the 2,3′,4,4′5-pentaCB (CB118), CB153, and 2,3,3′,4,4′5-hexaCB (CB156) congeners, we conducted PCB-CYP (CYP1A1, CYP1A2, CYP2A6, and CYP2B6) docking simulation by in silico analysis. The docking models showed that human CYP1A1, CYP2A6, and CYP2B6 isozymes have the potential to metabolize CB118 and CB153. On the other hand, it was inferred that CB156 is difficult to be metabolized by these four CYP isozymes. These results indicate that CYP1 and CYP2 isozymes may be involved in the characteristic accumulation patterns of PCB congeners in the blood of Yusho patients.

DOI： 10.1007/s11356-017-9498-z

Scopus

PubMed

researchmap

Language：Japanese   Publisher：(一社)日本毒性学会  

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Academic Press Inc.  

Triclosan (TCS), a commonly used antimicrobial compound, has recently been detected in the eggs of wild avian species. Exposure to TCS in rodents is known to interfere with thyroid hormone (TH), disrupt immune responses and cause liver disease. However, no attempt has been made to clarify the effects of TCS in avian species. The aim of this study is therefore to evaluate the toxic effects of in ovo exposure to TCS and explore the molecular mechanism by transcriptome analysis in the embryonic liver of a model avian species, chicken (Gallus gallus). Embryos were treated with graded concentration of TCS (0.1, 1 and 10 μg/g egg) at Hamburger Hamilton Stage (HHS) 1 (1st day), followed by 20 days of incubation to HHS 46. At the administration of 10 μg TCS/g egg, embryo mortality increased from 20% in control to 37% accompanied with 8% attenuation in tarsus length. While liver somatic index (LSI) in TCS treatments was enhanced, statistical difference was only observed at the treatment of 0.1 μg TCS/g egg in females. The up-regulation of several crucial differentially expressed genes (DEGs) in transcriptome analysis suggested that TCS induced xenobiotic metabolism (e.g. CYP2C23a, CYP2C45 and CYP3A37 in males
CYP2C45 in females) and activated the thyroid hormone receptor (THR) - mediated downstream signaling (e.g. THRSPB and DIO2 in males
THRSPB in females). In females, TCS may further activate the lipogenesis signaling (e.g. ACSL5, ELOVL2) and repress the lipolysis signaling (e.g. ABHD5, ACAT2). A battery of enriched transcription factors in relation to these TCS-induced signaling and phenotypes were found, including activated SREBF1, PPARa, LXRa, and LXRb in males and activated GLI2 in females
COUP-TFII was predicted to be suppressed in both genders. Finally, we developed adverse outcome pathways (AOPs) that provide insights into the molecular mechanisms underlying the alteration of phenotypes.

DOI： 10.1016/j.taap.2018.03.026

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY  

Proteome variation among natural populations along an environmental gradient may provide insights into how the biological functions of species are related to their local adaptation. We investigated protein expression in five stream stonefly species from four geographic regions along a latitudinal gradient in Japan with varying climatic conditions. The extracted proteins were separated by two-dimensional gel electrophoresis and identified by matrix-assisted laser desorption/ionization of time-of-flight (MALDI TOF/TOF), yielding 446 proteins. Low interspecies variation in the proteome profiles was observed among five species within geographical regions, presumably due to the co-occurring species sharing the environments. However, large spatial variations in protein expression were found among four geographic regions, suggesting strong regulation of protein expression in heterogeneous environments, where the spatial variations were positively correlated with water temperature. We identified 21 unique proteins expressed specifically in a geographical region and six common proteins expressed throughout all regions. In warmer regions, metabolic proteins were upregulated, whereas proteins related to cold stress, the photoperiod, and mating were downregulated. Oxygen-related and energy-production proteins were upregulated in colder regions with higher altitudes. Thus, our proteomic approach is useful for identifying and understanding important biological functions related to local adaptations by populations of stoneflies.

DOI： 10.1002/arch.21422

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ACADEMIC PRESS INC ELSEVIER SCIENCE  

The occurrence of antimicrobial agent triclosan (TCS) in the global aquatic and terrestrial environment is an emerging concern. While risk assessment for TCS is available in certain countries, no studies have attempted to assess the risk of TCS worldwide. This could be due to lack of method to characterize the global exposure. The present study therefore proposed a probabilistic-based approach to approximate the percent-ranked measured environmental concentrations (MECs) by estimating exposure concentration distribution (ECD) for different environmental compartments on a global scale, incorporating approximate 1200 single MECs. Hazard of TCS was assessed from species sensitivity distribution as well as predicted no effect concentrations (PNECs) derived from ecotoxicological and toxicological endpoints. We draw on experiences from previous risk assessment exercises and present a holistic approach for characterizing the risk of TCS to microorganism in sewage treatment plant, aquatic and soil organisms, avian and mammalian species, and humans. Using the approach, we estimated risk of TCS to organisms dwelling in sediment and living in surface waters, and the risk quotients (MEC/PNEC) were within the range of 0.95-33.3 and 0.49-9.5, respectively. While the risk quotients for other environmental compartments were below a value of 1, there are large uncertainties likely due to an insufficient dataset of exposure and hazard of TCS.

DOI： 10.1016/j.ecoenv.2017.05.020

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCI LTD  

This study investigated the accumulation of polybrominated diphenyl ethers (PBDEs) and their hydroxylated and methoxylated analogues (OH-PBDEs and MeO-PBDEs) in the blood of harbor porpoises, Dall's porpoises, and finless porpoises stranded or bycaught in Japanese coastal waters and in the North Pacific Ocean. Moreover, we suggested the origins of these contaminants and the factors affecting their pattern of accumulation. Levels of PBDEs in Dall's porpoises were one order of magnitude greater than those in the other species. OH-PBDE and MeO-PBDE levels were comparable to those of PBDEs. However, no correlation was found between the levels of OH-PBDEs and PBDEs, whereas a strong correlation was found between that of OH-PBDEs and MeO-PBDEs (p < 0.001). 6OH-BDE47, reported compound bio-synthesized by marine low-trophic level organisms, was the dominant congener. These results suggest that PBDEs found in these porpoise species derive from flame retardants, but OH-PBDEs and MeO-PBDEs are mainly of natural origins. (C) 2016 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.marenvres.2016.11.004

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER HEIDELBERG  

Dioxins cause various toxic effects through the aryl hydrocarbon receptor (AHR) in vertebrates, with dramatic species and strain differences in susceptibility. Although inbred mouse strains C3H/HeJ-lpr/lpr (C3H/lpr) and MRL/MpJ-lpr/lpr (MRL/lpr) are known as dioxin-sensitive and dioxin-resistant mice, respectively, the molecular mechanism underlying this difference remains unclear. The difference in the hepatic proteome of the two mouse strains treated with vehicle or 2,3,7,8-tetrabromodibenzo-p-dioxin (TBDD) was investigated by a proteomic approach of two-dimensional electrophoresis (2-DE) coupled with matrix-assisted laser desorption/ionization time-of-flight/time-of-flight tandem mass spectrometry (MALDI-TOF/TOF). To confirm the strain-difference in response to TBDD treatment, cytochrome P450 (CYP) 1A1 and 1A2 protein levels were measured in both strains. A dose of 10 A mu g/kg body weight of TBDD induced hepatic CYP1A1 and CYP1A2 expression in both strains, but the expression levels of both CYP1A proteins were higher in C3H/lpr mice than in MRL/lpr mice, supporting that C3H/lpr mice are more sensitive to dioxins than MRL/lpr mice. Proteins that were more induced or suppressed by TBDD treatment in C3H/lpr mice were successfully identified by 2-DE and MALDI-TOF/TOF, including proteins responsible for AHR activation through production of endogenous ligands such as aspartate aminotransferase, indolethylamine N-methyltransferase, and aldehyde dehydrogenases, as well as proteins reducing oxidative stress, such as superoxide dismutase and peroxiredoxins. Taken together, our results provide insights into the molecular mechanism underlying the high dioxin susceptibility of the C3H/lpr strain, in which AHR activation by TBDD is more prompted by the production of endogenous ligands, but the adaptation to oxidative stress is also acquired.

DOI： 10.1007/s00204-016-1834-4

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER HEIDELBERG  

The toxic effects of dioxins and related compounds (DRCs) are mediated by the aryl hydrocarbon receptor (AHR). Our previous study identified AHR1 and AHR2 genes from the red seabream (Pagrus major). Moreover, we found that AHR2 mRNA levels were notably elevated by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure in the early life stage of red seabream embryos, while AHR1 mRNA level was not altered. In this study, to investigate the regulatory mechanism of these AHR transcripts, we cloned and characterized 5'-flanking regions of AHR1 and AHR2 genes. Both of the 5'-flanking regions in these AHR genes contained three potential xenobiotic-responsive elements (XREs). To assess whether the 5'-flanking region is transactivated by rsAHR1 and rsAHR2 proteins, we measured the transactivation potency of the luciferase reporter plasmids containing the 5'-flanking regions by AHR1 and AHR2 proteins that were transiently co-expressed in COS-7. Only reporter plasmid (pGL4-rsAHR2-3XREs) that contained three putative XRE sites in the 5'-flanking region of AHR2 gene showed a clear TCDD dose-dependent transactivation by AHR1 and AHR2 proteins. TCDD-EC50 values for the rsAHR2-derived XRE transactivation were 1.3 and 1.4 nM for AHR1 and AHR2, respectively. These results suggest that the putative XREs of AHR2 gene have a function for AHR1- and AHR2-mediated transactivation, supporting our in ovo observation of an induction of AHR2 mRNA levels by TCDD exposure. Mutations in XREs of AHR2 gene led to a decrease in luciferase induction. Electrophoretic mobility shift assay showed that XRE1, the closest XRE from the start codon in AHR2 gene, is mainly responsible for the binding with TCDD-activated AHR. This suggests that TCDD-activated AHR1 and AHR2 up-regulate the AHR2 mRNA levels and this auto-induced AHR2 may amplify the signal transduction of its downstream targets including CYP1A in the red seabream.

DOI： 10.1007/s00204-016-1732-9

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

Aryl hydrocarbon receptor (AHR) is well conserved from invertebrates to vertebrates, and it mediates the toxic effects of exogenous ligands, including dioxins. Recent studies reported that AHRs activated by endogenous ligands play critical roles in mammalian physiological homeostasis. Avian species possess at least two AHR isoforms (AHR1 and AHR2), which exhibit species-and isoform-specific transactivation potencies to exogenous ligands, whereas mammals possess a single AHR. To delineate the profiles and roles of endogenous ligands for avian AHR isoforms, we investigated in vitro transactivation potencies of avian AHRs (AHR1 and AHR2 from the jungle crow, Corvus macrorhynchos; common cormorant, Phalacrocorax carbo; and black-footed albatross, Phoebastria nigripes) treated with the endogenous tryptophan metabolites 6-formylindolo [3,2-b] carbazole (FICZ), L-kynurenine (L-Kyn), kynurenic acid (KYNA), and indoxyl sulfate (IS). Furthermore, we analyzed the binding mode of these ligands to each avian AHR isoform by in silico docking simulations. The EC50 of FICZ (0.009-0.032 nM) was similar regardless of the species or isoform of AHR. The estimated in silico binding mode of FICZ to AHRs was well conserved in both isoforms. The transactivation potencies of avian AHRs to other tryptophan metabolites were 10(5)-10(7) fold lower than those for FICZ, and EC50 values varied in a species and isoform-specific manner. This was consistent with poor conservation of the binding mode of L-Kyn, KYNA, and IS predicted in in silico docking simulations. Our results suggest that in avian species, FICZ is the most potent endogenous AHR ligand, and that AHR1 and AHR2 are physiologically functional. (C) 2016 Published by Elsevier Inc.

DOI： 10.1016/j.cbpc.2016.03.011

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE BV  

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) induces a broad spectrum of toxic effects including craniofacial malformation and neural damage in fish embryos. These effects are mainly mediated by the aryl hydrocarbon receptor (AHR). However, the mode of action between TCDD-induced AHR activation and adverse outcomes is not yet understood. To provide a comprehensive picture of the AHR signaling pathway in fish embryos exposed to TCDD, red seabream (Pagrus major) embryos were treated with graded concentrations of TCDD (0.3-37 nM) in seawater, or with a mixture of TCDD and 500 nM CH223191, an AHR-specific antagonist. The transcriptome of red seabream embryos was analyzed using a custom-made microarray with 6000 probes specifically prepared for this species. A Jonckheere-Terpstra test was performed to screen for genes that demonstrated altered mRNA expression levels following TCDD exposure. The signals of 1217 genes (as human homologs) were significantly altered in a TCDD concentration-dependent manner (q-value < 0.2). Notably, the TCDD-induced alteration in mRNA expression was alleviated by co-exposure to CH223191, suggesting that the mRNA expression level of these genes was regulated by AHR. To identify TCDD-activated pathways, the microarray data were further subjected to gene set enrichment analysis (GSEA) and functional protein-protein interaction (PPI) network analysis. GSEA demonstrated that the effects of TCDD on sets of genes involved calcium, mitogen-activated protein kinase (MAPK), actin cytoskeleton, chemokine, T cell receptor, melanoma, vascular endothelial growth factor (VEGF), axon guidance, and renal cell carcinoma signaling pathways. These results suggest the hypotheses that TCDD induces immunosuppression via the calcium, MAPK, chemokine, and T cell receptor signaling pathways, neurotoxicity via VEGF signaling, and axon guidance alterations and teratogenicity via the dysregulation of the actin cytoskeleton and melanoma and renal cell carcinoma signaling pathways. Furthermore, the PPI network analysis indicated that the adverse outcome pathways of TCDD in the embryos might be propagated through several hub genes such as cell division control protein 42, phosphoinositide-3-kinase regulatory subunit 1, and guanine nucleotide binding proteins. Understanding these pathways potentially allows for exploring the adverse outcome pathway of the effects of TCDD on the red seabream embryos. (C) 2016 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.aquatox.2016.05.014

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：NATURE PUBLISHING GROUP  

The aryl hydrocarbon receptor (AHR) mediates dioxin toxicities. Several studies have suggested that two amino acid residues corresponding to the 324th and 380th positions in the ligand binding domain (LBD) of the chicken AHR1 (Ile_Ser as high sensitivity, Ile_Ala as moderate sensitivity, and Val_Ala as low sensitivity), could be an important factor determining dioxin sensitivity in avian species. Here, we analyzed the association between ecological factors and AHR1 LBD genotypes of 113 avian species. Cluster analyses showed that 2 major clusters and sub-clusters of the cluster 3 were associated with specific AHR1 genotypes depending on the food, habitat, and migration of the animal. The majority of the species with Ile_Ala type were the Passeriformes, which are omnivorous or herbivorous feeders in the terrestrial environment. The species with Val_Ala type was primarily composed of raptors and waterbirds, which have been exposed to naturally occurring dioxins. An in vitro reporter gene assay revealed that the sensitivity to a natural dioxin, 1,3,7-tribromodibenzo-p-dioxin was in the order of Ile_Ser > Ile_Ala > Val_Ala. These results suggest that ecological factors related to the exposure of natural dioxins contribute to natural selection of the avian AHR1 genotype, which consequently leads to different sensitivity to man-made dioxins.

DOI： 10.1038/srep27526

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER HEIDELBERG  

The associations of four single nucleotide polymorphisms (p.Arg194Trp, p.Arg280His, p.Pro206Pro, and p.Arg399Gln) in X-ray repair cross-complementing group 1 with urinary arsenic metabolites and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were investigated in a Vietnamese population (n = 100). Individuals with genotype AA in p.Pro206Pro showed significantly higher urinary monomethylarsonic acid (MMA(V)) and lower dimethylarsinic acid (DMA(V))/MMA(V) ratio than genotype AG. As for p.Arg399Gln, both Arg/Arg homozygous subjects and Arg/Gln heterozygous individuals showed a significantly higher urinary inorganic As percentage and lower 8-OHdG concentrations than Gln/Gln homozygous. Our results suggested that Arg399Gln is a functional SNP that may be related to DNA repair activity.

DOI： 10.1007/s00204-015-1490-0

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

There are growing concerns about the increase in hyperthyroidism in pet cats due to exposure to organo-halogen contaminants and their hydroxylated metabolites. This study investigated the blood contaminants polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) and their hydroxylated and methoxylated derivatives (OH-PCBs, OH-PBDEs, and MeO-PBDEs), in pet dogs and cats. We also measured the residue levels of these compounds in commercially available pet foods. Chemical analyses of PCBs and OH-PCBs showed that the OH-PCB levels were 1 to 2 orders of magnitude lower in cat and dog food products than in their blood, suggesting that the origin of OH-PCBs in pet dogs and cats is PCBs ingested with their food. The major congeners of OH-/MeO-PBDEs identified in both pet food products and blood were natural products (60H-/MeO-BDE47 and 2'OH-/MeO-BDE68) from marine organisms. In particular, higher concentrations of 60H-BDE47 than 2'OH-BDE68 and two MeO-PBDE congeners were observed in the cat blood, although MeO-BDEs were dominant in cat foods, suggesting the efficient biotransformation of 60H-BDE47 from 6MeO-BDE47 in cats. We performed in vitro demethylation experiments to confirm the biotransformation of MeO-PBDEs to OH-PBDEs using liver microsomes. The results showed that 6MeO-BDE47 and 2'MeO-BDE68 were demethylated to 60H-BDE47 and 2'OH-BDE68 in both animals, whereas no hydroxylated metabolite from BDE47 was detected. The present study suggests that pet cats are exposed to MeO-PBDEs through cat food products containing fish flavors and that the OH-PBDEs in cat blood are derived from the CYP-dependent demethylation of naturally occurring MeO-PBDE congeners, not from the hydroxylation of PBDEs.

DOI： 10.1021/acs.est.5b04216

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

The aim of this study was to understand the cytochrome P450 (CYP)-dependent metabolic pathway and potency of polychlorinated biphenyls (PCBs) in the Baikal seal (Pusa sibirica). In vitro metabolism of 62 PCB congener mixtures was investigated by using liver microsomes of this species. A decreased ratio of over 20% was observed for CB3, CB4, CB8, CB15, CB19, CB22, CB37, CB54, CB77, and CB105, suggesting the preferential metabolism of low-chlorinated PCBs by CYPs. The highly activated metabolic pathways in Baikal seals that were predicted from the decreased PCBs and detected hydroxylated PCBs (OH-PCBs) were CB22 to 4'OH-CB20 and CB77 to 4'OH-CB79. The total amount of OH-PCBs detected as identified and unidentified congeners accounted for only a 3.8 +/- 1.7 mol % of loaded PCBs, indicating many unknown PCB metabolic pathways. To explore factors involved in CYP-dependent PCB metabolism, we examined the relationships among the structural and physicochemical properties of PCBs, the in silica PCB-CYP docking parameters, and the in vitro PCB decreased ratios by principal component analysis. Statistical analysis showed that the decreased PCB ratio was at least partly accounted for by the substituted chlorine number of PCBs and the distance from the CI-unsubstituted carbon of docked PCBs to the heme Fe in CYP2A and 2B.

DOI： 10.1021/acs.est.5b03890

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER HEIDELBERG  

The aryl hydrocarbon receptor (AHR) is responsible for susceptibility to its ligand-dependent responses. However, the effect of non-AHR factors is less clear. To explore the non-AHR factors, we used two mouse strains with different AHR genetic variants, namely C3H/lpr and MRL/lpr strains with Ala and Val as the 375th amino acid residue, respectively. To assess the contribution of AHR alone, COS-7 cells transiently expressing AHR from each strain were treated with 6-formylindolo[3,2-b]carbazole (FICZ) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and xenobiotic-responsive element (XRE)-driven reporter gene activities were measured. FICZ-EC50 values for the C3H/lpr and MRL/lpr AHR-mediated transactivation were 0.023 and 0.046 nM, respectively, indicating a similar susceptibility in both AHR genotypes. In contrast, C3H/lpr AHR was fourfold more sensitive to TCDD than MRL/lpr AHR. By a pull-down assay using a XRE-containing PCR product as bait and the hepatic nuclear extracts of both FICZ-treated mouse strains, we identified two interacting proteins as heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP-A2) and its splicing variant (hnRNP-A2b). Immunoprecipitation assays demonstrated the AHR interaction with hnRNP-A2/B1. When hnRNP-A2 was co-expressed with the MRL/lpr or C3H/lpr AHR in COS-7, FICZ treatment decreased EC50 to about threefold in both AHR genotypes, compared with EC50 in AHR alone. Similarly, hnRNP-A2b co-expression also lowered the FICZ-EC50 values. In TCDD-treated COS-7, responses depended on the AHR genotype; while no change in TCDD-EC50 was observed for C3H/lpr AHR when hnRNP-A2 was co-expressed, the value was reduced to nearly tenfold for MRL/lpr AHR. Co-transfection with hnRNP-A2b attenuated the AHR sensitivity to TCDD. In conclusion, the hnRNP-A2/B1 interacting with AHR may be a modulator of the AHR ligand sensitivity.

DOI： 10.1007/s00204-014-1352-1

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ACADEMIC PRESS INC ELSEVIER SCIENCE  

The concentrations of polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and their hydroxylated metabolites (OH-PCBs and OH-PBDEs) were measured in the blood of Eurasian wild pigs (Sus scrofa) from a municipal waste open dumping site (DS) and a reference site (RS) in South India. We showed that contamination with OH-PCBs was higher in female pigs from the DS than in all other adult pigs. The highest OH-PCB concentrations were found in piglets from the DS. Moreover, the hepatic expression levels of CYP1A and CYP2B were higher in piglets than in their dam, implying metabolism of PCBs by cytochrome P450 (CYP) enzymes. The OH-PCB congener profiles differed according to sex and collection sites, possibly because of variations in the expression levels of phase I and phase II enzymes among individual pigs, differences in the exposure sources, and maternal transfer of parent PCBs. The hepatic CYP1A expression levels were positively correlated with the blood concentrations of 4OH-CB107, 4OH-CB162, and 4OH-CB187, implying CYP1A-dependent formation of these OH-PCBs in the pig liver. We found no significant correlations between the blood concentrations of OH-PCBs and thyroid hormones (THs); however, the thyroxin (T-4) levels were lower in pigs from the DS than in pigs from the RS. Our limited dataset suggest that induced CYP enzymes accelerate the metabolism of xenobiotics and endogenous molecules in pigs. Thus, besides parental compounds, the risk of hydroxylated metabolites entering wildlife and humans living in and around municipal open waste dumping sites should be considered. (C) 2015 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.envres.2015.02.012

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

The aryl hydrocarbon receptor (AHR) mediates toxic responses to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and other dioxin-like cornpounds (DLCs). Avian species possess multiple AHR isoforms (AHR1, AHR1,6, and AHR2) that exhibit species- and isoform-specific responses to ligands. To account for the ligand preference in terms of the structural features of avian AHRs, we generated in silico homology models of the ligand-binding domain of avian AHRs based on ho/o human HIF-2 alpha (PDB entry 3H7VV). Molecular docking simulations of TCDD and other DLCs with avian AHRls and AHR2s using ASEDock indicated that the interaction energy increased with the number of substituted chlorine atoms in congeners, supporting AHR transactivation potencies and World Health Organization TCDD toxic equivalency factors of congeners. The potential interaction energies of an endogenous AHR ligand, 6-formylindolo [3,2-b] carbazole (FICZ) to avian AHRs were lower than those of TCDD, which was supported by a greater potency of FICZ for in vitro AHR-mediated transactivation than TCDD. The molecular dynamics simulation revealed that mean square displacements in Ile324 and Ser380 of TCDD-bound AHR1 of the chicken, the most sensitive species to TCDD, were smaller than those in other avian AHR1s, suggesting that the dynamic stability of these amino acid residues contribute to TCDD preference. For avian AHR2, the corresponding residues (Val/Ser or Val/Ala type) were not responsible for differential TCDD sensitivity. Application of the three-dimensional reference interaction site model showed that the stabilization of TCDD binding to avian AHRs may be due to the solvation effect depending on the characteristics of two amino acids corresponding to Ile324 and Ser380 in chicken AHR1. This study demonstrates that in silica simulations of AHRs and ligands could be used to predict isoform-, ligand-, and species-specific interactions.

DOI： 10.1021/es505733f

Web of Science

Scopus

PubMed

researchmap

Publishing type：Research paper (scientific journal)   Publisher：Japanese Society for Hygiene  

Arsenic metabolism affects the susceptibility of humans to arsenic toxicity; therefore, clarification of the factors associated with individual variations in arsenic metabolism is an important task. Genetic polymorphisms such as single nucleotide polymorphisms (SNPs) in arsenic (+3 oxidation state) methyltransferase (AS3MT), which can methylate arsenic compounds using S-adenosyl-l-methionine (AdoMet), have been reported to modify arsenic methylation. In this review, we summarize studies conducted by us in Vietnam and by others on the association of AS3MT genetic polymorphisms with arsenic metabolism as well as human health effects. Most of the SNPs in AS3MT showed inconsistent results in terms of genotype-dependent differences in arsenic metabolism among the studies. However, AS3MT 12390 (rs3740393) and 14458 (rs11191439) were consistently related to arsenic methylation regardless of the study population: AS3MT 12390 (rs3740393) affected the second step of methylation of arsenic, whereas 14458 (rs11191439) affected the first methylation step.

DOI： 10.1265/jjh.70.186

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER IRELAND LTD  

The haptoglobin (HP) gene deletion allele (HPdel) is responsible for anhaptoglobinemia and a genetic risk factor for anaphylaxis reaction after transfusion due to production of the anti-HP antibody. The distribution of this allele has been explored by several groups including ours. Here, we studied the frequency of HPdel in addition to the distribution of common HP genotypes in 293 Vietnamese. The HPdel was encountered with the frequency of 0.020. The present result suggested that this deletion allele is restricted to East and Southeast Asians. Thus, this allele seems to be a potential ancestry informative marker for these populations. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.legalmed.2014.08.004

Web of Science

Scopus

PubMed

researchmap

Language：Japanese   Publisher：The Japanese Society of Toxicology  

DOI： 10.14869/toxpt.42.1.0_S9-6

researchmap

Publishing type：Research paper (scientific journal)   Publisher：Elsevier  

© 2015 Elsevier B.V. This study aimed to elucidate the catalytic function of cytochrome P450 (CYP) 1 enzymes in aquatic mammals. Alkoxyresorufin O-dealkylation (AROD) activities including methoxy- (MROD), ethoxy- (EROD), pentoxy- (PROD), and benzyloxyresorufin O-dealkylation (BROD), and 2- and 4-hydroxylation activities of 17β-estradiol (E2) were measured by using yeast-expressed Baikal seal (Pusa sibirica) CYP1A1, 1A2, and 1B1 proteins. Heterologous protein expression of the Baikal seal CYP1s (bsCYP1s) in yeast microsomes was confirmed by reduced CO-difference spectra and immunoblotting. Heterologously expressed human CYP1 enzyme (hCYP1) activities were simultaneously measured and compared with those of bsCYP1 isozymes. Recombinant bsCYP1A1 protein showed the highest Vmaxof EROD, followed by MROD, PROD, and BROD, similar to that of hCYP1A1. Vmax/Kmratios of all AROD activities catalyzed by bsCYP1A1 were lower than those catalyzed by hCYP1A1, suggesting less potential for AROD by bsCYP1A1. Enzymatic assays for bsCYP1A2 showed no or minimal AROD activities, while hCYP1A2 displayed MROD and EROD activities. bsCYP1B1 showed an AROD profile (EROD>BROD>MROD»PROD) similar to that of hCYP1B1; however, Vmax/Kmratios of all AROD activities by bsCYP1B1 were higher. Yeast microsomes containing bsCYP1A1 and 1B1 and hCYP1A1, 1A2, and 1B1 metabolized E2to 2-OHE2and 4-OHE2, whereas bsCYP1A2 showed no such activity. Comparison of 4- and 2-hydroxylations of E2by CYP1As suggests that bsCYP1A1, hCYP1A1, and 1A2 preferentially catalyze 2- rather than 4-hydroxylation. As for CYP1B1, the Vmax/Kmratios suggest that both Baikal seal and human CYPs catalyze 4- rather than 2-hydroxylation. Interspecies comparison showed that bsCYP1B1 has higher metabolic potencies for both E2hydroxylations than does hCYP1B1, whereas the activity of bsCYP1A1 was lower than that of hCYP1A1. Messenger RNA expression levels of bsCYP1s in the liver of Baikal seals indicated that bsCYP1A1 and 1A2 enzymes contributed to 16.2% and 83.7% of total CYP1s, respectively; bsCYP1B1 accounted for only 0.06%. Addition of anti-human CYP1A1 antibody in seal liver microsomes suppressed EROD activity more than did anti-human CYP1A2 antibody. Therefore, EROD may be catalyzed by hepatic bsCYP1A1 but not bsCYP1A2, consistent with the results of yeast-expressed bsCYP1A1 and 1A2. In silico substrate-docking models of bsCYP1s suggested that the defect in bsCYP1A2 enzymatic activities may be accounted for by the Pro substitution of highly conserved Thr in the I-helix, which is involved in formation of a hydrogen bond with the hydroperoxy intermediate on the heme. This Thr-Pro substitution is evolutionarily conserved across aquatic mammals and could explain their lower metabolic potential for persistent organic pollutants.

DOI： 10.1016/j.aquatox.2015.03.010

Scopus

PubMed

researchmap

Publishing type：Research paper (scientific journal)   Publisher：Japanese Society for Hygiene  

DOI： 10.1265/jjh.70.186

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

We have previously reported that high accumulation of dioxins and related compounds induced cytochrome P450 (CYP 1s) isozymes in the liver of wild Baikal seals, implying the enhanced hydroxylation of polychlorinated biphenyls (PCBs). The present study attempted to elucidate the residue concentrations and patterns of PCBs and hydroxylated PCBs (OH-PCBs) in the livers of Baikal seals. The hepatic residue concentrations were used to assess the potential effects of PCBs and OH-PCBs in combination with the analyses of serum thyroid hormones, hepatic mRNA levels, and biochemical markers. The hepatic expression levels of CYP1 genes were positively correlated with the concentration of each OH-PCB congener. This suggests chronic induction of these CYP1 isozymes by exposure to PCBs and hydroxylation of PCBs induced by CYP 1s. Hepatic mRNA expression monitoring using a custom microarray showed that chronic exposure to PCBs and their metabolites alters the gene expression levels related to oxidative stress, iron ion homeostasis, and inflammatory responses. In addition, the concentrations of OH-PCBs were negatively correlated with l-thyroxine (T-4) levels and the ratios of 3,3',5-triiodo-l-thyronine (T-3)/reverse 3,3',5'-triiodo-l-thyroninee (rT(3)). These observations imply that Baikal seals contaminated with high levels of OH-PCBs may undergo the disruption of mechanisms related to the formation (or metabolism) of T-3 and T-4 in the liver.

DOI： 10.1021/es5043386

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

We have previously demonstrated that Baikal seals (Pusa sibirica) are still being exposed to polychlorinated biphenyls (PCBs), and the population is at risk. In the present study, we measured the residue levels of PCBs and their hydroxylated metabolites (OH-PCBs) in the blood of Baikal seals and assessed the impact of OH-PCBs on the thyroid function. Blood concentrations of PCBs and OH-PCBs were in the range of 2.8130 ng g(-1) wet wt. and 0.71-4.6 ng g(-1) wet wt., respectively. Concentrations of higher-chlorinated OH-PCBs (hexa- to octa-PCBs) were more than 70% to total OH-PCB concentrations, indicating Baikal seals are mostly risked by higher-chlorinated OH-PCBs. High levels of 4OH-CB146 and 4OH-CB187 and low levels of 4OH-CB107/4'OH-CB108 found in Baikal seals were different from those in other phocidae species, suggesting the unique drug-metabolizing enzyme activities and/or contamination sources in this species. Concentrations of some OH-PCBs in males were significantly higher than those in females. These results suggest that these isomers may be preferentially transferred from mother to pup via cord blood. However, concentrations of almost all the isomers were not significantly correlated with the levels of blood total T3 and T4, implying less impact of PCB-related compounds on the thyroid hormone circulation. (C) 2014 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.chemosphere.2014.03.089

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ACADEMIC PRESS INC ELSEVIER SCIENCE  

Hepatic concentrations of persistent organochlorines (OCs) were determined in the common minke whale (Balaenoptera acutorostrata) from the North Pacific. To investigate the effects of OCs on the transcriptome in the minke whale, the present study constructed a hepatic oligo array of this species where 985 unique oligonucleotides were spotted and further analyzed the relationship between the OC levels and gene expression profiles of liver tissues. The stepwise multiple linear regression analysis identified 32 genes that correlated with hepatic OC levels. The mRNA expression levels of seven cytochrome P450 (CYP) genes, CYP1A1, 1A2, 208, 2E1, 3A72, 4A35, and 4V6 showed no clear correlations with the concentration of each OC, suggesting that the accumulated OCs in the liver did not reach levels that could alter CYP expression. Among the genes screened by the custom oligo array analysis, hepatic mRNA expression levels of 16 genes were further measured using quantitative real-time reverse transcription polymerase chain reaction. The mRNA levels of vitamin D-binding protein (DBP) were negatively correlated with non-ortho coplanar polychlorinated biphenyl (PCB) levels. Androgen receptor-associated coregulator 70 (ARA70) expression levels showed a significant positive correlation with concentrations of non-ortho coplanar PCB169. These correlations suggest that coplanar PCB-reduced DBP expression could suppress vitamin D receptor-mediated signaling cascades in peripheral tissues. Alternatively, the suppression of vitamin D receptor signaling cascade could be enhanced through competition with the androgen receptor signaling pathway for ARA70. In addition, a negative correlation between kynureninase and PCB169 levels was also observed, which suggest an enhanced accumulation of an endogenous aryl hydrocarbon receptor agonist, kynurenine in the minke whale population. Further studies are necessary to translate the changes in the transcriptome to toxicological outcomes including the disruption of the nervous and immune systems. (C) 2014 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.ecoenv.2014.06.028

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE BV  

The toxicity of dioxins such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is mainly mediated by an aryl hydrocarbon receptor (AHR), which regulates the transcription of multiple target genes including cytochrome P450 1A (CYP1A). Our pervious study identified the presence of TCDD-induced defects of peripheral nerve projection in red seabream (Pagrus major) embryos. However, it remains unclear whether the TCDD-induced peripheral neurotoxicity is mediated by the AHR. To assess the contribution of the red seabream AHR (rsAHR) signaling pathway to the neuronal toxicity, red seabream embryos at 10 h post-fertilization (hpf) were treated for 80 min with TCDD (0, 0.3, 5.3, and 37 nM in seawater) alone or in combination with CH223191 (500 nM in seawater), which is an AHR antagonist. A preliminary in vitro reporter gene assay confirmed that TCDD-induced transcriptional activity via rsAHR1 and rsAHR2 was suppressed by CH223191 treatment in a dose-dependent manner. CYP1A mRNA expression in embryos was determined by 2-step real time quantitative-polymerase chain reaction at 24 and 120 hpf and in situ hybridization at 48, 72, 96 and 120 hpf. The morphology of the peripheral nerve system (PNS) was also microscopically observed by fluorescent staining using an anti-acetylated tubulin antibody at 120 hpf. CYP1A mRNA expression was dose-dependently induced by TCDD at all of the examined developing stages. The suppression of TCDD-induced CYP1A expression by CH223191 treatment was observed in embryos at 24 and 48 hpf, while the effect of the rsAHR antagonist disappeared at 96 and 120 hpf. This phenomenon indicated the transient suppression of TCDD-induced rsAHR activation by CH223191 treatment. The immunostaining of peripheral nerves at 120 hpf demonstrated that the projections of the craniofacial nerve were altered in TCDD-treated embryos, and the frequency of TCDD-induced abnormal projections was not prevented by co-treatment with CH223191. These results indicate that the transient suppression of TCDD-induced rsAHR activation during the early developing stages of the red seabream does not influence the abnormal projection of peripheral nerves. In conclusion, transient rsAHR activation in the early stages of development is not involved in the neurotoxicity. (C) 2014 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.aquatox.2014.05.001

Web of Science

Scopus

PubMed

researchmap

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Dioxins including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) cause toxic effects through activation of the aryl hydrocarbon receptor (AHR)-mediated signaling pathway. Our previous studies have investigated the function of 2 AHR isoforms (AHR1 and AHR2) in avian species and identified a third AHR in the chicken (Gallus gallus) genome. Knowledge of multiple avian AHRs is indispensable to understand molecular mechanisms of AHRmediated toxic effects and establish risk assessment framework for environmental AHR ligands in avian species. In this study, we successfully isolated a third novel AHR1-like cDNA from chicken and designated it as chicken AHR1 beta (ckAHR1β). The mRNA expression of ckAHR1β was primarily detected in the liver, and the hepatic protein expression was confirmed by Western blotting. Although mRNA expression of ckAHR1β was not altered by in ovo TCDD exposure, ckAHR1β exhibited specific binding to [3H] TCDD, TCDD-dependent nuclear translocation, and interaction with xenobiotic responsive elements (XREs) and AHR nuclear translocators (ARNTs). In vitro XRE-driven reporter gene assays revealed ckAHR1β-mediated transactivation of TCDD in a dosedependent manner, showing a 10-fold reduced sensitivity (high EC50) compared with that mediated by ckAHR1. The mutation of Val371 to Ser371 in the ligand-binding domain of ckAHR1β shifted the TCDD-EC50 toward the value observed in ckAHR1, indicating the critical roles of the amino acid in sensitivity. Furthermore, ckAHR1β-mediated transactivation of TCDD was enhanced by 17β-estradiol (E2)-activated chicken estrogen receptor a (ckERa), suggesting a positive cross talk between ckERa and ckAHR1β signaling pathway. Both TCDD-induced and its enhanced activities by E2 were suppressed by the ckAHR repressor in a manner similar to ckAHR1. Collectively, our findings discover the role of ckAHR1β in dioxin toxicity and give an insight into the evolutionary history of the AHR signaling pathway. © The Author 2013. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved.

DOI： 10.1093/toxsci/kft192

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：OXFORD UNIV PRESS  

A 1,000-fold difference has been reported in dioxin sensitivity between avian species. This difference is because the 2 amino acids in the type 1 aryl hydrocarbon receptor (AhR1), at positions 325 and 381, correspond to Leu324 and Ser380 in chickens. The chicken had been reported to be the only avian species to possess a sensitive form of AhR1. This is the first study to reveal that the ostrich (Struthio camelus), a nonchicken species, also has a pair of amino acids (Ile-325 and Ser-381) that show high ligand affinity. However, the alignment of the AhR1 cDNA sequence showed that the AhR sequence in the ostrich was different than that of other avian species even though the critical amino acids were observed at positions 325 and 381. Ostrich AhR1 was also evaluated in a heterologous expression study. Ostrich AhR1 showed very high transcriptional activity of the cytochrome P450 1A5 (CYP1A5) gene in African Green Monkey Cercopithecus aethiops kidney cells (COS-7) treated with Sudan III. In primary cultures of ostrich kidney cells, CYP1A5 expression was induced by Sudan III at a lower (or almost identical) concentration to that observed in the chicken. The present study revealed a new AhR ligand sensitive avian species (i.e., the ostrich).

DOI： 10.3382/ps.2013-03090

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

Our line of papers revealed that the common (great) cormorant (Phalacrocorax carbo) possesses two isoforms of the aryl hydrocarbon receptor (ccAHR1 and ccAHR2). This paper addresses in vitro tests of the ccAHR signaling pathways to solve two questions: (1) whether there are functional differences in the two ccAHR isoforms, and (2) whether a molecular perturbation, cytochrome P450 1A (ccCYP1A) induction, in the population-level can be predicted from the in vitro tests. The transactivation potencies mediated by ccAHR1 and ccAHR2 were measured in COS-7 cells treated with 15 selected dioxins and related compounds (DRCs), where ccAHR1 or ccAHR2 expression plasmid and ccCYP1A5 promoter/enhancer-linked luciferase reporter plasmid were transfected. For congeners that exhibited dose-dependent luciferase activities, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) relative potencies (REPs) and induction equivalency factors (IEFs) were estimated. ccAHR1-IEF profile was similar to WHO avian TCDD toxic equivalency factor (TEF) profile except for dioxin-like polychlorinated biphenyls that showed lower IEFs in ccAHR1-driven reporter assay. ccAHR2-IEF profile was different from WHO TEFs and ccAHR1-IEFs. Notably, 2,3,4,7,8-PeCDF was more potent than TCDD for ccAHR2-mediated response. Using ccAHR1- and ccAHR2-IEFs and hepatic DRC concentrations in the Lake Biwa cormorant population, total TCDD induction equivalents (IEQs) were calculated for each ccAHR-mediated response. Nonlinear regression analyses provided significant sigmoidal relationships of ccAHR1- and ccAHR2-derived IEQs with hepatic ccCYP1A5 mRNA levels, supporting the results of in vitro ccAHR-mediated TCDD dose-response curves. Collectively, our in vitro AHR reporter assay potentially could be an alternative to molecular epidemiology of the species of concern regarding CYP1A induction by AHR ligands.

DOI： 10.1021/es401155g

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

To evaluate species- and isoform-specific responses to dioxins and related compounds (DRCs) via aryl hydrocarbon receptor (AHR) in the red seabream (Pagrus major), we constructed a reporter gene assay system. Each expression plasmid of red seabream AHR1 (rsAHR1) and AHR2 (rsAHR2) together with a reporter plasmid containing red seabream CYP1A 5'-flanking region were transfected into COS-7 cells. The cells were treated with graded concentrations of seven DRC congeners including 2,3,7,8-TCDD, 1,2,3,7,8-PeCDD, I,2,3,4,7,8-HxCDD, 2,3,7,8-TCDF, 2,3,4,7,8-PeCDF, 1,2,3,4,7,8-HxCDF, and PCB126. Both rsAHR1 and rsAHR2 exhibited dose-dependent responses for all the tested congeners. The rsAHR isoform-specific TCDD induction equivalency factors (rsAHR1- and rsAHR2-IEFs) were calculated on the basis of 2,3,7,8-TCDD relative potency derived from the dose response of each congener. The rsAHR1-IEFs of PeCDD, HxCDD, TCDF, PeCDF, and HxCDF were estimated as 0.17, 0.29, 2.5, 1.5, and 0.27, respectively. For PCB126, no rsAHR1-IEF was given because of less than 10% 2,3,7,8-TCDD maximum response. The rsAHR2-IEFs of PeCDD, HxCDD, TCDF, PeCDF, HxCDF, and PCB 126 were estimated as 0.38, 0.13, 1.5, 0.93, 0.20, and 0.0085, respectively. The rsAHR1/2-IEF profiles were different from WHO toxic equivalency factors for fish. In silico docking simulations supported that both rsAHRs have potentials to bind to these congeners. These results suggest that dioxin toxicities may be mediated by both rsAHRs in red seabreams.

DOI： 10.1021/es304423w

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

Concentrations of persistent organochlorine compounds (OCs) including polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs) in the liver and adipose tissue of Japanese cadavers were measured, and their toxicokinetics were examined in association with hepatic cytochrome P450 (CYP) 1A protein expression levels. Total 2,3,7,8-tetrachlorodibenzo-p-dioxin toxic equivalents (TEQs) were 66 +/- 74 and 65 +/- 57 pg/g lipid weight (mean +/- S.D.) in the liver and adipose tissue, respectively. Total PCBs (sum of 62 congeners targeted), p,p'-dichlorodiphenyl-dichloroethylene (p,p'-DDE) and beta-hexachlorocyclohexane (beta-HCH) were detected at concentrations over 1 mu g/g lipid in both tissues of some specimens. For most of the dioxin-like congeners, total PCBs, p,p'-DDE, oxychlordane, alpha- and beta-HCH, hexachlorobenzene (HCB), and tris(4-chlorophenyl)methane (TCPMe), age-dependent increases in concentrations were found in the adipose tissue of males. No such age-dependent trend was observed in the liver, suggesting that there are different mechanisms underlying the hepatic concentrations of OCs. Immunoblot analyses indicated detectable expression of hepatic CYP1A2 protein, whereas no CYP1A1 protein was detected. The CYP1A2 expression levels were positively correlated with concentrations (on wet weight basis) of 2,3,4,7,8-P5CDF, the dominant TEQ-contributed congeners in the liver, indicating the induction of this CYP. Hepatic CYP1A2 protein levels were strongly correlated with the liver to adipose concentration (L/A) ratios of PCDD/F congeners with more than 5 chlorine atoms. Together with higher concentrations of the congeners in the liver than in the adipose tissue, the observation on L/A ratios of highly chlorinated PCDD/Fs suggests that induced hepatic CYP1A2 protein is involved in their sequestration in this human population, as observed in model animals (rodents). Nonetheless, the magnitude of hepatic sequestration (L/A ratio) of PCDD/Fs in this human population was lower than in other mammals and birds, reported previously. This study emphasizes the fact that toxicokinetics of some OCs can be affected at least partly by CYP1A2 protein levels in humans. For the extrapolation of their toxicokinetics from model animals to humans, knowledge on the induction and sequestration potencies of CYP1A is necessary. (C) 2013 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.envint.2012.12.008

Web of Science

Scopus

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE BV  

We investigated 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced effects on the morphology of peripheral nervous system (PNS) in the developing red seabream (Pagrus major) embryos. The embryos at 10 h post-fertilization (hpf) were treated with 0, 0.1, 0.4 or 1.7 mu g/L of TCDD in seawater for 80 min. The morphology of PNS was microscopically observed with florescence staining using an anti-acetylated tubulin antibody at 48, 78, 120 and 136 hpf. Axon length of facial nerve (VII) was found to be shortened by TCDD exposure. Axon guidance in the glossopharyngeal nerve (IX) and vagus nerve (X) was altered at 120 and 136 hpf in a TCDD dose-dependent manner. Lowest observable effect level of TCDD (0.1 mu g/L) that induced the morphological alteration of PNS was lower than those of other endpoints on morphological deformities so far reported. Given that the growth cone at the tip of growing nerve axons advances under the influence of its surrounding tissues, we hypothesized that TCDD exposure would affect (1) the nerve cell proliferation/differentiation, (2) the structure of muscle as an axon target and (3) the nerve guidance factor in the embryos. By the immunostaining of embryos with an antibody against the neuronal specific RNA-binding protein, HuD, and an antibody against the sarcomeric myosin, no morphological effects were observed on the neural proliferation/differentiation and the structure of facial muscles of TCDD-treated embryos. In contrast, whole mount in situ hybridization of semaphorin 3A (Sema3A), a secretory axon repulsion factor, revealed the altered expression pattern of its transcripts in TCDD-treated embryos. Our findings suggest that TCDD treatment affects the projection of PNS in the developing red seabream embryos through the effects on the axonal growth cone guidance molecule such as Sema3A, but not On the neuronal differentiation/proliferation and axon target. The PNS in developing embryos may be one of the most sensitive biomarkers to the exposure of dioxin-like compounds. (c) 2012 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.aquatox.2012.12.009

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：OXFORD UNIV PRESS  

The constitutive androstane receptor (CAR) not only displays a high basal transcriptional activity but also acts as a ligand-dependent transcriptional factor. It is known that CAR exhibits different ligand profiles across species. However, the mechanisms underlying CAR activation by chemicals and the species-specific responses are not fully understood. The objectives of this study are to establish a high-throughput tool to screen CAR ligands and to clarify how CAR proteins from the Baikal seal (bsCAR) and the mouse (mCAR) interact with chemicals and steroid receptor coactivator 1 (SRC1). We developed the surface plasmon resonance (SPR) system to assess quantitatively the interaction of CAR with potential ligands and SRC1. The ligand-binding domain (LBD) of bsCAR and mCAR was synthesized in a wheat germ cellfree system. The purified CAR LBD was then immobilized on the sensor chip for the SPR assay, and the kinetics of direct interaction of CARs with ligand candidates was measured. Androstanol and androstenol, estrone, 17-estradiol, TCPOBOP, and CITCO showed compound-specific but similar affinities for both CARs. The CAR-SRC1 interaction was ligand dependent but exhibited a different ligand profile between the seal and the mouse. The results of SRC1 interaction assay accounted for those of our previous in vitro CAR-mediated transactivation assay. In silico analyses also supported the results of CAR-SRC1 interaction; there is little structural difference in the ligand-binding pocket of bsCAR and mCAR, but there is a distinct discrimination in the helix 11 and 12 of these receptors, suggesting that the interaction of ligand-bound CAR and SRC1 is critical for determining species-specific and ligand-dependent transactivation over the basal activity. The SPR assays demonstrated a potential as a high-throughput screening tool of CAR ligands.

DOI： 10.1093/toxsci/kfs288

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

This study focuses on gender-specific accumulation features of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/DFs) and dioxin-like polychlorinated biphenyls (DL-PCBs) in common (great) cormorants (Phalacrocorax carbo) collected from Lake Biwa, Japan. Male cormorants showed a tendency to have higher levels of PCDD/DFs and DL-PCBs than did females. For PCDDs, the male-to-female concentration ratio (M/F ratio) for each congener significantly decreased with the liver-to-muscle concentration ratio (Li/Mu ratio). For PCDFs, there also was a weak negative relationship between Li/Mu ratio and M/F ratio. In contrast, for DL-PCBs, M/F ratios showed no correlation with Li/Mu ratios, but increased with an increase in lipophilicity. These results, together with observations from prior studies, suggest that congener-specific hepatic sequestration may be a factor limiting the maternal transfer of PCDDs and, to a lesser extent, PCDFs. Maternal transfer of DL-PCBs seems to favor more lipophilic congeners in the cormorants. © 2013 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.envpol.2013.03.001

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCI LTD  

To validate the outcome of the national regulation on dioxins emission implemented in 1999, this study investigated temporal trends of chlorinated dioxins and related compounds (DRCs) in liver of common cormorants (Phalacrocorax carbo) collected from Lake Biwa, Japan between 2001 and 2008, as a part of the "Survey on the State of Dioxins Accumulation in Wildlife" conducted by the Ministry of the Environment, Japan. We also measured a biomarker of DRCs exposure, the cytochrome P450 1A (CYP1A)-dependent O-dealkylation activity of alkoxyresorufins (AROD), including methoxy-, ethoxy-, pentoxy- and benzyloxy-resorufins in the samples over 2001-2007. Neither TEQ nor AROD activity showed any clear declining trend over the time period, although the emission of DRCs during the corresponding period was estimated to be apparently decreasing. Our data indicate that the concentration of recalcitrant DRCs in the cormorant during 2001-2008 was scarcely affected by the national regulation on dioxins emission. (c) 2012 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.envpol.2012.04.014

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

BACKGROUND: The human FUT2 gene encodes a secretor-type a(1,2)fucosyltransferase, and many population-specific polymorphisms have been reported in the coding region. STUDY DESIGN AND METHODS: Direct sequencing, real-time polymerase chain reaction, and high-resolution melt (HRM) analysis were done to detect single-nucleotide polymorphism (SNPs) and copy number variations (CNVs) in a Vietnamese population. The impacts of two novel mutations on the encoded enzyme were examined by a transient expression study. RESULTS: The major nonfunctional allele in the 294 Vietnamese was se357,385, whereas no CNV was detected. Two novel SNPs, 818C>A (Thr273Asn) and 853G>A (Ala285Thr), distributed at low frequency, were shown to remarkably affect the enzyme activity. CONCLUSION: The allelic polymorphism of FUT2 in Vietnamese is similar to that of other East and Southeast Asian populations. This result may reflect the history and gene flow of this population. In addition, HRM analysis seems to be a simple and effective method for screening rare SNPs of FUT2 in a large number of samples. [Correction statement added after online publication 21-Dec-2011: Thr273Ala has been updated to Thr273Asn throughout.]

DOI： 10.1111/j.1537-2995.2011.03485.x

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

Some wild populations of fish-eating birds and raptors are exposed to high concentrations of 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) and related compounds such as other 2,3,7,8-substituted polychlorinated dibenzop- dioxins and polychlorinated dibenzofurans and coplanar polychlorinated biphenyls, resulting in accumulation in their tissues. It has been demonstrated that TCDD-like chemicals cause toxic effects via aryl hydrocarbon receptor (AHR)-mediated signaling pathways. The aim of this study was to characterize the AHR from the peregrine falcon (Falco peregrines) to predict its sensitivity to TCDD-like chemicals. The AHR1, AHR2, and AHR nuclear translocator 1 of the peregrine falcon are more similar in amino acid sequence to avian species less sensitive to TCDD-like chemicals such as the cormorant (95%) than to more sensitive species such as the chicken (90%). From the amino acid sequence, it is likely that the ligand-binding affinity of peregrine falcon AHR1 and AHR2 would be very low compared with the chicken or other sensitive species, and it was actually proved by an in vitro reporter gene assay. We concluded that the peregrine falcon, one of raptor species, may be relatively resistant to TCDD-like chemicals.

DOI： 10.1007/s10344-011-0559-1

Web of Science

Scopus

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

To assess possible impacts of environmental pollutants on gene expression profiles in a variety of organisms, we developed a novel differential display system with primer sets that are common in seven vertebrate species, based on degenerate oligonucleotide-primed PCR (DOP-PCR). An 8-mer inverse repeat motif was found in most transcripts from the seven vertebrates including fish to primates with detailed transcriptome information; more than 10 000 motifs were recognized in common in the transcripts of the seven species. Among them, we selected 275 common motifs that cover about 40-70% of transcripts throughout these species, and designed 275 DOP-PCR primers that were common to seven vertebrate species (common DOP-PCR primers). To detect genes responsive to 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD) in developing embryos, differential display with common DOP-PCR primers was applied to embryonic liver of two avian species, the chicken (Gallus gallus) and the common cormorant (Phalacrocorax carbo), which were exposed in OVO to TCDD. The cDNA bands that showed differences between the control and TCDD-treated groups were sequenced and the mRNA expression levels were confirmed by real-time RT-PCR This approach succeeded in isolating novel dioxin-responsive genes that include 10 coding genes in the chicken, and 1 coding gene and 1 unknown transcript in the cormorant, together with cytochrome P450 1As that have, already been well established as dioxin markers. These results highlighted the usefulness of systematically designed novel differential display systems to search genes responsive to chemicals in vertebrates, including wild species, for which transcriptome information is not available.

DOI： 10.1021/es201085m

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

Our previous studies have detected high levels of dioxins and related compounds (DRCs) including polychlorinated dibenzo-p-dioxins (PCDDs), furans (PCDFs), and coplanar PCBs (Co-PCBs) in the black-footed albatross (BFA), Phoebastria nigripes, from the North Pacific region. We have also cloned two aryl hydrocarbon receptors, AHR1 and AHR2, of the BFA. To evaluate the sensitivity to DRCs in the BFA and to assess the stain the wild population, this study investigated the mRNA expression status of cytochrome P450 1A (CYP1A) induction levels of BFA AHR1 and AHR2 and also the transactivation potencies of each AHR by 15 selected DRC congeners. Quantitative real-time PCR of BFA AHR mRNAs showed that hepatic AHR1 is more highly expressed than AHR2. Transactivation by graded concentrations of individual DRCs was measured in COS-7 cells, where BFA AHR1 or AHR2 was transiently transfected. For congeners that exhibited AHR-mediated dose-dependent activities, 50% effective concentration (EC50) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) relative potencies (REPs) were estimated. Based on the estimates of the REPs, TCDD induction equivalency factors (IEFs) were determined. For BFA AHR1, PeCDF was equipotent to TCDD, but other congeners exhibited lower IEFs. For BFA AHR2, PCDD/F congeners except OCDD/F showed IEFs >= 1.0. Using BFA AHR1- or AHR2-IEFs and hepatic concentrations of DRCs in North Pacific BFAs, TCDD induction equivalents (IEQs) were calculated. We further constructed nonlinear regression models on the relationships between BFA AHR1- or AHR2-IEF derived total IEQ or WHO-TEF derived total TEQ and ethoxyresorufin-O-deethylase activity (EROD) in the liver of wild BFAs. The results indicated that the relationships of BFA AHR1- and AHR2-based IEQs and EROD were predictable from BFA AHR1- and AHR2-mediated transactivation by TCDD, respectively. Collectively, these results suggest that the in vitro assay incorporating the AHR of species of concern would be a useful tool to predict the sensitivity to DRCs in the species and CYP1A induction in the wild population.

DOI： 10.1021/es2028263

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ROYAL SOC CHEMISTRY  

We investigated the association of As exposure and genetic polymorphism in glutathione S-transferase pi 1 (GSTP1) with As metabolism in 190 local residents from the As contaminated groundwater areas in the Red River Delta, Vietnam. Total As concentrations in groundwater ranged from <0.1 to 502 mu g l(-1). Concentrations of dimethylarsinic acid (DMA(V)), monomethylarsonic acid (MMA(V)), and arsenite (As(III)) in human urine were positively correlated with total As levels in the groundwater, suggesting that people in these areas may be exposed to As through the groundwater. The concentration ratios of urinary As(III) /arsenate (As(V)) and MMA(V) /inorganic As (IA; As(III) + As(V))(M/I), which are indicators of As metabolism, increased with the urinary As level. Concentration and proportion of As(III) were high in the wild type of GSTP1 Ile105Val compared with the hetero type, and these trends were more pronounced in the higher As exposure group (>56 mu g l(-1) creatinine in urine), but not in the lower exposure group. In the high As exposure group, As(III)/As(V) ratios in the urine of wild type of GSTP1 Ile105Val were significantly higher than those of the hetero type, while the opposite trend was observed for M/I. These results suggest that the excretion and metabolism of IA may depend on both the As exposure level and the GSTP1 Ile105Val genotype.

DOI： 10.1039/c1mt00133g

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

Thyroid hormones (THs) are essential for the regulation of growth and development in both humans and wildlife. Until recently, TH concentrations in the tissues of animals have been examined by immunoassay (IA) methods. IA methods are sensitive, but for TH analysis, they are compromised by a lack of adequate specificity. In this study, we determined the concentrations of six THs, L-thyroxine (T-4), 3,3',5-triiodo-L-thyronine (T-3), 3,3',5'-triiodo-L-thyronine (rT(3)), 3,5-diiodo-L-thyronine (3,5-T-2), 3,3'-diiodo-L-thyronine (3,3'-T-2), and 3-iodo-L-thyronine (3-T-1), in the serum of humans (n = 79) and wild Baikal seals (n = 37), by isotope ([C-13(6)]-T-4)dilution liquid chromatography (LC)-tandem mass spectrometry (MS/MS), and compared the TH levels with those measured by an electrochemiluminescent immunoassay (ECLIA) method. T-3 and T-4 were detected in all serum samples of both humans and Baikal seals, whereas T-1, 3,3'-T-2, and 3,5-T-2 were below the limit of detection (LOD). rT(3) was detected in Baikal seal sera at concentrations higher than T-3 in 28 seal samples, indicating an anomaly in deiodinase activity in Baikal seals. In humans, regression analyses of TH concentrations, measured by ECLIA and LC-MS/MS methods, showed significant correlations for T-4 (r = 0.852) and T-3 (r = 0.676; after removal of a serum sample with abnormal T-3 levels). In Baikal seals, a low correlation coefficient (r = 0.466) for T-4 levels and no correlation for T-3 levels (p = 0.093) were found between ECLIA and LC-MS/MS methods. These results suggest that interference by a nonspecific reaction against anti-T-3 and anti-T-4 antibodies used in the ECLIA can contribute to inaccuracies in TH measurement in Baikal seals. When the relationship between concentrations of THs in sera and dioxin-like toxic equivalents in blubber samples of Baikal seals (n = 19) was examined, a significantly negative correlation was found for serum T-4 levels measured by the LC-MS/MS method, but not for those measured by ECLIA. Thus, our results indicate that the LC-MS/MS method is more reliable and accurate for the elucidation of alteration in circulating TH levels in wildlife, as caused by environmental and physiological factors.

DOI： 10.1021/es203002a

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ACADEMIC PRESS INC ELSEVIER SCIENCE  

Arsenic causes DNA damage and changes the cellular capacity for DNA repair. Genes in the base excision repair (BER) pathway influence the generation and repair of oxidative lesions. Single nucleotide polymorphisms (SNPs) in human 8-oxoguanine DNA glycosylase (hOGG1) Ser326Cys; apurinic/apyrimidinic endonuclease (APE 1) Asp148Glu; X-ray and repair and cross-complementing group 1 (XRCC1) Arg280His and Arg399Gln in the BER genes were analyzed, and the relationship between these 4 SNPs and the urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) concentrations of 100 Vietnamese population exposed to arsenic was investigated. Individuals with hOGG1 326Cys/Cys showed significantly higher urinary 8-OHdG concentrations than did those with 326 Ser/Cys and Ser/Ser. As for APE1 sp148Glu, heterozygous subjects showed significantly higher urinary 8-OHdG concentrations than did those homozygous for Asp/Asp. Moreover, global ethnic comparison of the allelic frequencies of the 4SNP5 was performed in 10 population and previous reported data. The mutant allele frequencies of hOGG1 Ser326Cys in the Asian populations were higher than those in the African and Caucasian populations. As for APE1 Asp148Glu, Caucasians showed higher mutant frequencies than those shown by African and Asian populations. Among Asian populations, the Bangladeshi population showed relatively higher mutant allele frequencies of the APE1 Asp148Glu polymorphism. This study is the first to demonstrate the existence of genetic heterogeneity in a worldwide distribution of SNPs (hOGG1 Ser326Cys, APE1 Asp148Glu, XRCC1 Arg280His, and XRCC1 Arg399Gln) in the BER genes. Published by Elsevier Inc.

DOI： 10.1016/j.taap.2011.08.007

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE BV  

We have previously indicated that accumulation of chlorinated dioxins and related compounds (DRCs) induced cytochrome P450 (CYP) 1A1, 1A2 and 1B1 isozymes in the liver of wild Baikal seals (Pusa sibirica). Here we attempt to assess the potential effects of DRCs triggered by the induction of these CYP1 isozymes in this species, using an integrative approach, combining gene expression monitoring and biochemical assays. To screen genes that may potentially respond to the exposure of DRCs, we constructed a custom cDNA oligo array that can target mRNAs in Baikal seals, and monitored hepatic mRNA expression levels in the wild population. Correlation analyses between the hepatic total 2,3,7,8-tetrachlorodibenzo-p-dioxin toxic equivalents (TEQs) and mRNA levels supported our previous findings that high accumulation of DRCs induces the transcription of CYP1A1, CYP1A2 and CYP1B1 genes. In addition, our integrative assessment indicated that the chronic exposure to DRCs may alter the hepatic transcript levels of genes related to oxidative stress, Fe ion homeostasis, and inflammatory responses. The expression levels of CYP1A2 showed significant positive correlations with levels of malondialdehyde, a biomarker of lipid peroxidation, and of etheno-dA, a DNA adduct, suggesting that the lipid peroxidation may be enhanced through the production of reactive oxygen species (ROS) triggered by CYP1A2 induction. Moreover, there was a positive correlation between heme oxygenase activities and malondialdehyde levels, suggesting the prompted hems degradation by ROS. Fetuin-A levels, which are suppressed by inflammation, showed a significant negative correlation with TEQ levels, and hepcidin levels, which are conversely increased by inflammation, had significant positive correlations with malondialdehyde and etheno-dA levels, implying the progression of inflammation by DRC-induced oxidative stress. Taken together, we propose here that wild Baikal seals may suffer from effects of chronic exposure to DRCs on the induction of CYP1 isozymes, followed by increased oxidative stress, heme degradation and inflammation. (C) 2011 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.aquatox.2011.05.007

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

Body distribution and growth- and nutritional status-dependent accumulation of 21 trace elements were investigated in harbor seals (Phoca vitulina) stranded in the North Sea coast in 2002. Higher concentrations and burdens of Mn, Se, Mo, Ag, Sn, Hg, and Bi in the liver, Cd in the kidney, As in the blubber, and Co, Sr, and Ba in the bone were observed. Significant positive correlations of hepatic Se, Mo, Ag, Cd, Sn, Hg, Tl, and Bi with standard body length were found, while significant negative relationships were detected for Mn, As, Rb, Sr, and Sb in the liver. Concentrations of Co, Se, Sr, Sn, Hg, and Bi in the liver, V. Sr, Ag, Sn, and Hg in the kidney, V. Mn, Co, Rb, Sr, Sn, Ba, and Pb in the blubber increased with decreasing blubber thickness of harbor seals, indicating enrichment of these elements in the target tissue by emaciation. (C) 2011 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.marpolbul.2011.02.047

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

Cytochrome P450 CYP2 family enzymes are important in a variety of physiological and toxicological processes. CYP2 genes are highly diverse and orthologous relationships remain clouded among CYP2s in different taxa. Sequence and expression analyses of CYP2 genes in diapsids including birds and reptiles may improve understanding of this CYP family. We sought CYP2 genes in a liver cDNA library of the common cormorant (Phalacrocorax carbo), and in the genomes of other diapsids, chicken (Gallus gallus), zebra finch (Taeniopygia guttata), and anole lizard (Anolis carolinensis), for phylogenetic and/or syntenic analyses. Screening of the cDNA library yielded four CYP2 cDNA clones that were phylogenetically classified as CYP2C45, CYP2J25, CYP2AC1, and CYP2AF1. There are numerous newly identified diapsid CYP2 genes that include genes related to the human CYP2Cs, CYP2D6, CYP2G2P, CYP2J2, CYP2R1, CYP2U1, CYP2W1, CYP2AB1P, and CYP2AC1P. Syntenic relationships show that avian CYP2Hs are orthologous to CYP2C62P in humans. CYP2C23 in rats, and Cyp2c44 in mice, and suggest that avian CYP2Hs, along with human CYP2C62P and mouse Cyp2c44, could be renamed as CYP2C23, based upon the nomenclature rules. Analysis of sequence and synteny identifies cormorant and finch CYPs that are apparent orthologs of phenobarbital-inducible chicken CYP2C45. Transcripts of all four cormorant CYP2 genes were detected in the liver of birds from Lake Biwa, Japan. The transcript levels bore no significant relationship to levels of chlorinated organic pollutants in the liver, including polychlorinated biphenyls and dichlorodiphenyltrichloroethane and its metabolites. In contrast, concentrations of perfluorooctane sulfonate and perfluorononanoic acid were negatively correlated with levels of CYP2C45 and/or CYP2J25, suggesting down-regulation of expression by these environmental pollutants. This study expands our view of the phylogeny and evolution of CYP2s, and provides evolutionary insight into the chemical regulation of CYP2 gene expression in diapsids including birds. (C) 2010 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.cbpc.2010.11.006

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

The present study assessed the transactivation potencies of the Baikal seal (Pusa sibirica) peroxisome proliferator-activated receptor alpha (BS PPAR alpha) by perfluorochemicals (PFCs) having various carbon chain lengths (C4-C12) using an in vitro reporter gene assay. Among the twelve PFCs treated with a range of 7.8-250 mu M concentration, eight perfluoroalkyl carboxylates (PFCAs) and two perfluoroalkyl sulfonates (PFSAs) induced BS PPAR alpha-mediated transcriptional activities in a dose-dependent manner. To compare the BS PPARa. transactivation potencies of PFCs, the present study estimated the PFOA induction equivalency factors (IEFs), a ratio of the 50% effective concentration of PFOA to the concentration of each compound that can induce the response corresponding to 50% of the maximal response of PFOA. The order of IEFs for the PFCs was as follows: PFOA (IEF: 1) > PFHpA (0.89) > PENA (0.61) > PFPeA (0.50) > PFHxS (0.41) > PFHxA (0.38) approximate to PFDA (0.37) > PFBA (0.26) = PFOS (0.26) > PFUnDA (0.15) >> PFDoDA and PFBuS (not activated). The structure-activity relationship analysis showed that PFCAs having more than seven perfluorinated carbons had a negative correlation (r = -1.0, p = 0.017) between the number of perfluorinated carbons and the IEF of PFCAs, indicating that the number of perfluorinated carbon of PFCAs is one of the factors determining the transactivation potencies of the BS PPARa. The analysis also indicated that PFCAs were more potent than PFSAs with the same number of perfluorinated carbons. Treatment with a mixture of ten PFCs showed an additive action on the BS PPARa. activation. Using IEFs of individual PFCs and hepatic concentrations of PFCs in the liver of wild Baikal seals, the PFOA induction equivalents (IEQs, 5.3-58 ng IEQ/g wet weight) were calculated. The correlation analysis revealed that the hepatic total IEQ showed a significant positive correlation with the hepatic expression levels of cytochrome P450 4A-like protein (r = 0.53, p = 0.036). This suggests that our approach may be useful for assessing the potential PPARa-mediated biological effects of complex mixtures of PFCs in wild Baikal seal population.

DOI： 10.1021/es103748s

Web of Science

Scopus

PubMed

researchmap

Language：English   Publisher：MDPI AG  

Individual variations in inorganic arsenic metabolism may influence the toxic effects. Arsenic (+3 oxidation state) methyltransferase (AS3MT) that can catalyze the transfer of a methyl group from S-adenosyl-L-methionine (AdoMet) to trivalent arsenical, may play a role in arsenic metabolism in humans. Since the genetic polymorphisms of AS3MT gene may be associated with the susceptibility to inorganic arsenic toxicity, relationships of several single nucleotide polymorphisms (SNPs) in AS3MT with inorganic arsenic metabolism have been investigated. Here, we summarize our recent findings and other previous studies on the inorganic arsenic metabolism and AS3MT genetic polymorphisms in humans. Results of genotype dependent differences in arsenic metabolism for most of SNPs in AS3MT were Inconsistent throughout the studies. Nevertheless, two SNPs, AS3MT 12390 (rs3740393) and 14458 (rs11191439) were consistently related to arsenic methylation regardless of the populations examined for the analysis. Thus, these SNPs may be useful indicators to predict the arsenic metabolism via methylation pathways.

DOI： 10.3390/ijms12042351

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

Our previous studies have provided evidence that birds have two isoforms of aryl hydrocarbon receptors (AHR1 and AHR2) and AHR nuclear translocators (ARNT1 and ARNT2) that potentially mediate toxic responses to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related compounds. We have also shown that while both in vitro-expressed chicken AHR1 (ckAHR1) and AHR2 (ckAHR2) exhibit binding affinities to TCDD, only ckAHR1 but not ckAHR2 showed a TCDD-dose-dependent transactivation potency of chicken cytochrome P450 1A5 (ckCYP1A5) in in vitro reporter gene assays. To explore the molecular mechanism of functional difference in the two ckAHRs, the present study investigated the molecular characteristics and function of chicken ARNT (ckARNT) that is a potential dimerization partner for the activation of ckAHR. The full-length ckARNT1 and ckARNT2 cDNAs were isolated and their alternative splice variants were also identified. The ckARNT1 transcript was ubiquitously expressed in various tissues, but ckARNT2 showed restricted expressions in brain, kidney and eye, indicating a similar expression pattern to mammalian ARNTs. The expressions of tagged-ckARNT1 and -ckARNT2 were confirmed in a chicken hepatoma LMH cells by western blot analyses, and their interactions with each ckAHR and a specific recognition DNA element, xenobiotic response element (XRE), were examined by gel shift assays. The result showed that ckARNT1 and ckARNT2 dimerize with each ckAHR isoform and bind with the XRE in a TCDD-dependent manner. Hence, we conclude that functional loss on the dimerization with ckARNTs or the XRE binding is not the major cause of the deficient TCDD-dependency of ckAHR2 for the transactivation. Furthermore, in vitro reporter gene assays showed that transfected ckARNT1 failed to modulate the transcriptional induction of ckAHR-mediated ckCYP1A5 gene by TCDD in COS-7 and LMH cells, whereas ckARNT2 could potentiate the TCDD-dependent response in COS-7 but not in LMH cells. This suggests that ckARNT2 has a distinct role from ckARNT1 in AHR signaling pathway and in a cell-specific mode of action. (C) 2010 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.cbpc.2010.11.005

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

To evaluate the sensitivity and responses to dioxins and related compounds (DRCs) via aryl hydrocarbon receptor (AHR) in Baikal seals (Pusa sibirica), we constructed an in vitro reporter gene assay system. Baikal seal AHR (BS AHR) expression plasmid and a reporter plasmid containing CYP1A1 promoter were transfected in COS-7 cells. The cells were treated with six representative congeners, and dose-dependent responses were obtained for all the congeners. EC(50) values of 2,3,7,8-TCDD, 1,2,3,7,8-PeCDD, 2,3,7,8-TCDF, 2,3,4,7,8-PeCDF, and PCB126 were found to be 0.021, 1.8, 0.16, 2.4, and 2.5 nM, respectively. As the response did not reach the maximal plateau, EC(50) value for PCB118 could not be obtained. The TCDD-EC(50) for BS AHR was as high as that for dioxin sensitive C57BL/6 mouse AHR. The in vitro dose responses were further analyzed following an established systematic framework and multiple (20, 50, and 80%) relative potencies (REPs) to the maximum TCDD response. The estimates revealed lower REP ranges (20-80%) of PeCDD and PeCDF for BS AHR than for mouse AHR. Average of the 20, 50, and 80% REPs was designated as Baikal seal specific TCDD induction equivalency factor (BS IEF). The BS LEFs of PeCDD, TCDF, PeCDF, PCB126, and PCB118 were estimated as 0.010, 0.018, 0.0078, 0.0059, and 0.00010, respectively. Total TCDD induction equivalents (IEQs) that were calculated using BS IEFs and hepatic concentrations in wild Baikal seals corresponded to only 12-31% of 2005 WHO TEF-derived TEQs. Nevertheless, about 50% of Baikal seals accumulated IEQs over the TCDD-EC(50) obtained in this study. This assessment was supported by the enhanced CYP1A1 mRNA expression found in 50% of the specimens contaminated over the TCDD-EC(50). These findings suggest that the IEFs proposed from this in vitro assay could be used to predict AHR-mediated responses in wild seals.

DOI： 10.1021/es102991s

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：OXFORD UNIV PRESS  

The aryl hydrocarbon receptor (AHR) repressor (AHRR) has been recognized as a negative feedback modulator of AHR-mediated responses in fish and mammals. However, the repressive mechanism by the AHRR has not been investigated in other animals. To understand the molecular mechanism of dioxin toxicity and the evolutionary history of the AHR signaling pathway in avian species, the present study addresses chicken AHRR (ckAHRR). The complementary DNA sequence of ckAHRR encodes an 84-kDa protein sharing 29-52% identities with other AHRRs. High levels of ckAHRR messenger RNA were recorded in the kidney and intestine of nontreated chicks. In hepatoma LMH cells, the 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD) 50% effective concentration value for ckAHRR induction (0.0016nM) was the same as that for chicken cytochrome P450 1A5 (ckCYP1A5), implying a shared transcriptional regulation of ckAHRR and ckCYP1A5 by chicken AHR (ckAHR). In ckAHRR transient transfection assays, ckAHRR repressed both ckAHR1- and ckAHR2-mediated transcriptional activities. Deletion and mutation assays revealed that basic helix-loop-helix/Per-ARNT-Sim A domains of ckAHRR, particularly 217-402 amino acid residues, are indispensable for the repression, but the AHR nuclear translocator sequestration by ckAHRR and SUMOylation of ckAHRR are not involved in its repressive mechanism. Additionally, subcellular localization assay of ckAHR1-enhanced green fluorescent protein fusion protein showed that ckAHRR did not affect nuclear translocation of the ckAHR1. Furthermore, ckAHRR inhibited the TCDD- and 17 beta estradiol-enhanced ckCYP1A5 transcription through AHR-estrogen receptor a (ER alpha) cross talk. Taken together, the function of AHRR is conserved in chicken in terms of the negative regulation of AHR and ER alpha activities, but its functional mechanism is likely distinct from those of the mammalian and fish homologues.

DOI： 10.1093/toxsci/kfq336

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

Arsenic trioxide (ATO) is an effective agent for acute promyelocytic leukemia (APL). In this study, the concentrations of dimethylarsinic acid (DMA), monomethylarsonic acid (MMA), As (V), As (III), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in urine and/or serum of a 4-year-old APL patient were followed during ATO treatment. In comparison with a similar analysis previously published for an 85-year-old APL patient, the levels of arsenic compounds and the percentages of MMA and DMA in the present child patient were lower than those of the old patient. Significant positive correlation of 8-OHdG was observed only with DMA, and not with other arsenic compounds. These results are quite different from those of our previous study on an old APL patient during ATO treatment. When arsenic poisoning is diagnosed, it seems important to take into account the differences in the arsenic metabolism according to the ages of subjects. This study is the first to show the relationship between the levels of 8-OHdG and arsenic compounds in urine of a child APL patient treated with ATO.

DOI： 10.1007/s11419-010-0104-z

Web of Science

Scopus

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

Nineteen trace elements were determined in liver, muscle, kidney, gonads, and hair of 18 harp seals (Phoca groenlandica) from Pangnirtung in the Baffin Island, Canada. Concentrations of V. Mn, Fe, Cu, Mo, Ag, and Hg in the liver, Co, Cd, and Tl in the kidney, and Ba and Pb in the hair were significantly higher than those in other tissues. Significant positive correlations between Hg concentrations in the hair, and liver, kidney and testis imply usefulness of the hair sample for non-destructive monitoring of Hg in the harp seals. It is suggested that whereas Hg preferentially accumulates in the liver, the accumulation in other tissues is induced at higher hepatic Hg levels. In contrast, Se may not be accumulated in other tissues compared with the liver even at higher hepatic Hg levels because of the presence of excess Se for Hg detoxification in other tissues (C) 2011 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.marpolbul.2011.02.022

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：CSIRO PUBLISHING  

We analysed arsenic (As) compounds in the stomach and intestine contents, bile and urine of green (Chelonia mydas) and hawksbill turtles (Eretmochelys imbricata) to understand As accumulation through intake and excretion. Stable isotopes of delta N-15 and delta C-13 were also measured for understanding the feeding behaviour dependent accumulation of As. Major As species in gastrointestinal contents were unknown water-soluble As, followed by unextracted As. Concentrations of AB and DMA in the tissues were higher than those in the stomach contents (prey items), indicating high bioaccumulation of these arsenicals. In green turtles, AB concentration was high in bile and increased throughout the gastrointestinal tract, suggesting significant biliary excretion of AB. delta N-15 was positively correlated with AB level in green turtles, whereas a negative relationship between residual As and delta N-15 was observed in hawksbill turtles. This study indicates feeding behaviour-dependent accumulation of As compounds in both turtle species for the first time.

DOI： 10.1071/EN10091

Web of Science

Scopus

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE BV  

Here we propose a novel microarray data analysis method applicable to evaluation of the chemical effects on wild animals First, we analyzed correlations between log-transformed hepatic 2,3,7,8-tetrachlorodibenzo-p-dioxin toxic equivalent (TEQ) levels and probe signals detected in wild cormorant liver to screen contaminant-responsive genes Second, principal component analysis (PCA) was conducted using the screened probes Third, these probes were divided into two groups based on our PCA result Finally, we calculated Euclidian distance of signals, which is equivalent to variance of gene expressions, in each probe set, and analyzed the relationship between log-transformed hepatic TEQ levels and Euclidian distances A probe set whereby the calculated Euclidian distance was positively correlated with TEQ levels, could indicate genes that were directly affected by dioxins or other persistent organic pollutants (POPs), hence they can be used as biomarkers By contrast, there were a number of probes whereby the Euclidian distance was negatively correlated with TEQ levels In the latter probe group, the smaller Euclidian distances in highly contaminated individuals could point to changes in physiological activities of wild cormorants Therefore, our microarray data analysis method will provide new insights into POPs-responsive genes in field-collected samples for toxicogenomics studies (C) 2010 Elsevier BV All rights reserved

DOI： 10.1016/j.scitotenv.2010.08.065

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

Our previous studies have isolated multiple isoforms of aryl hydrocarbon receptors (AHRs) and AHR nuclear translocators (ARNTs) in avian species. However, roles of such genes on cytochrome P450 1A (CYP1A) expression are not fully understood. To investigate the effects of dioxins on the hepatic expression profiles of AHR1, AHR2, ARNT1 and ARNT2 in avian species, and whether the expression levels of AHRs and ARNTs affect the transcriptions of CYP1A4 and CYP1A5 genes, the eggs of common (great) cormorants (Phalacrocorax carbo) collected from Lake Biwa, Japan, were in ovo administrated with 0, 1500 and 4500 pg/g egg of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and the hepatic expression levels of AHRs, ARNTs and CYP1As in embryos were monitored with two-step real-time RT-PCR. In young and adult cormorants collected from the same location, the hepatic expressions of these genes were also measured to understand the effects of growth stage. The residue levels of TCDD and other chlorinated dioxin-like congeners (DLCs) in the body of cormorants were quantified with high-resolution gas chromatography equipped with mass-spectrometry. There was no observable effect of in ovo TCDD treatment even at the highest dosage on mortality, body weight and morphology of the liver, heart, spleen, kidney and lung in the embryos. The mRNA expression of ARNT2 was slightly suppressed by the treatment with TCDD, while no alteration was observed for the expression of AHR1. AHR2 and ARNT1. Expressions of CYP1A4 and CYP1A5 were dose-dependently enhanced by TCDD, but CYP1A4 mRNA level increased more prominently than CYP1A5, indicating the difference in induction efficiency between the CYP1A isozymes. Comparison of hepatic mRNA levels of these genes among embryonic, young and adult cormorants revealed that young and adult cormorants had greater CYP1A5 expression levels than embryos, independently of the accumulation levels of DLCs. These results suggest that the hepatic induction of each CYP1A by DLCs in cormorants occurs in an isoform-specific manner and CYP1A5 expression, at least partially, depends on the factors related to the growth of cormorants, but the transcriptional processes of CYP1A5 are not related to the expression levels of AHRs and ARNTs. This study yielded results supporting our previous observations that in reality, high accumulation of DLCs induces hepatic CYP1A4 and 1A5 expressions in the wild cormorant population. (C) 2010 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.cbpc.2010.04.010

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：SETAC PRESS  

Dioxins and related compounds (DRCs) and perfluorinated compounds were measured in the livers of pigs (Sus scrofa) collected from an open waste dumping site in South India. Hepatic concentrations of DRCs and perfluorooctanesulfonate (PFOS; up to 200 ng/g wet wt) were significantly higher in male and female pigs, respectively, collected from the dumping site than in those from a reference site. Results suggest that dumping sites are a source of DRCs and PFOS. Hepatic concentrations of DRCs in piglets were higher than in mothers, especially for the congeners with molecular weights in the range of 360 to 400, implying congener-specific maternal transfer of DRCs in swine. Concentrations of polychlorinated dibenzo-p-dioxins and dibenzofurans and some non-ortho dioxin-like polychlorinated biphenyls (PCBs) in the liver of pigs were higher than those in the adipose fat and muscle of the same specimens. In addition, the liver-to-adipose concentration ratios for each congener had a significant positive correlation with the levels of hepatic cytochrome P450 (CYP)1A-like protein, suggesting congener-specific and CYP1A-dependent hepatic sequestration of DRCs in the swine. Total hepatic 2,3,7,8-tetrachlorodibenzo-p-dioxin toxic equivalents (TEQs; 8.9-350 pg/g fat wt) had a significant positive correlation with CYP1A-like protein expression (r= 0.56, p = 0.012), suggesting the induction of CYP1A by DRCs. However, the total TEQs had a significant negative correlation with CYP4A-like protein (r= -0.49, p= 0.029), suggesting repression of peroxisome proliferator-activated receptor-alpha (PPAR alpha)-mediated signaling pathway by DRCs. Decreases in plasma total thyroxine (T(4)), free T(4), and immunoglobulin (Ig) G were also found in pigs from the dumping site compared with those from the reference site. This study provides insight into the toxicological impacts of DRCs and perfluorinated compounds in wild animals from open waste dumping sites. Environ. Toxicol. Chem. 2010;29:1551-1560. (C) 2010 SETAC

DOI： 10.1002/etc.189

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

The present study assesses effects of dioxins and related compounds (DRCs) including polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, and dioxin-like polychlorinated biphenyls (DL-PCBs) on cytochrome P450 1A (CYP1A) expression level in liver of black-footed albatrosses (Phoebastria nigripes) collected from the North Pacific, Total 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-T4CDD) toxic equivalents (TEQs) derived from toxic equivalency factor for birds proposed by World Health Organization were in the range of 2100 to 10 000 pg/g lipid wt (120-570 pg/g wet wt). Simultaneously, microsomal alkoxyresorufin O-dealkylase (AROD) activities, including methoxy-, ethoxy-, pentoxy-, and benzyloxy-resorufin O-dealkylase activities were also measured in the same specimens. Total TEQs and TEQ (on wet wt basis) from some individual DRC congeners had significant positive correlations with AROD activities, suggesting induction of CYP1A by DRCs. Congeners like 2,3,7,8-T4CDD and most of the DL-PCBs that showed no significant positive correlations between the concentrations and AROD activities, exhibited significant negative correlations between AROD activities and the concentration ratio of the congener to a recalcitrant CB169, suggesting preferential metabolism of these congeners by induced CYP1A. As far as we know, this is the first direct evidence revealing that hepatic CYP1A level is elevated with the accumulation of DRCs in the wild black-footed albatross population. The present study gives more robust estimate of impacts of DRCs on CYP1A induction in this rare pelagic species than indexes like hazard quotient and TEQ-threshold comparison that have been so far carried out.

DOI： 10.1021/es1000177

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ACADEMIC PRESS INC ELSEVIER SCIENCE  

To elucidate the role of genetic factors in arsenic metabolism, we investigated associations of genetic polymorphisms in the members of glutathione S-transferase (GST) superfamily with the arsenic concentrations in hair and urine, and urinary arsenic profile in residents in the Red River Delta, Vietnam. Genotyping was conducted for CST omega 1 (GSTO1) A1a140Asp, Glu155del, Glu208Lys, Thr217Asn, and Ala236Val, GST omega 2 (GSTO2) Asn142Asp, CST pi 1 (GSTP1) Ile105Val, GST mu 1 (GSTM1) wild/null, and GST theta 1 (GSTT1) wild/null. There were no mutation alleles for GSTO1 Glu208Lys, Thr217Asn, and Ala236Val in this population. GSTO1 Glu 155del hetero type showed higher urinary concentration of As(V) than the wild homo type. Higher percentage of DMA(V) in urine of GSTM1 wild type was observed compared with that of the null type. Strong correlations between GSTP1 Ile105Val and arsenic exposure level and profile were observed in this study. Especially, heterozygote of GSTP1 Ile105Val had a higher metabolic capacity from inorganic arsenic to monomethyl arsenic, while the opposite trend was observed for ability of metabolism from As(V) to As(III). Furthermore, other factors including sex, age, body mass index, arsenic level in drinking water, and genotypes of As (+ 3 oxidation state) methyltransferase (AS3MT) were also significantly co-associated with arsenic level and profile in the Vietnamese. To our knowledge, this is the first study indicating the associations of genetic factors of CST superfamily with arsenic metabolism in a Vietnamese population. (C) 2009 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.taap.2009.11.007

Web of Science

Scopus

PubMed

researchmap

Language：English   Publisher：Walter de Gruyter GmbH  

In this review, we summarize the current knowledge on exposure, metabolism, and health effects of arsenic (As) in residents from As-contaminated groundwater areas of Vietnam and Cambodia based on our findings from 2000 and other studies. The health effects of As in humans include severe gastrointestinal disorders, hepatic and renal failure, cardiovascular disturbances, skin pigmentation, hyperkeratosis, and cancers in the lung, bladder, liver, kidney, and skin. Arsenic contamination in groundwater is widely present at Vietnam and Cambodia and the highest As levels are frequently found in groundwater from Cambodia. Sand filter system can reduce As concentration in raw groundwater. The results of hair and urine analyses indicate that residents from these As-contaminated areas are exposed to As. In general, sex, age, body mass index, and As exposure level are significantly associated with As metabolism. Genetic polymorphisms in arsenic (+III) methyltransferase and glutathione-5-transferase isoforms may be influenced As metabolism and accumulation in a Vietnamese population. It is suggested oxidative DNA damage is caused by exposure to As in groundwater from residents in Cambodia. An epidemiologic study on an association of As exposure with human health effects is required in these areas. © 2010 Freund Publishing House Limited.

DOI： 10.1515/REVEH.2010.25.3.193

Scopus

PubMed

researchmap

In: Hamamura, N., Suzuki, S., Mendo, S., Barroso, C.M., Iwata, H., Tanabe, S. (Eds.), Biological Responses to Chemical Contaminants: From Molecular to Community Level (Interdisciplinary Studies on Environmental Chemistry Vol. 3), Global COE Program, Ehime University, TERRAPUB, Tokyo

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

To characterize ligand-dependent transcriptional activation of constitutive active/androstane receptor (CAR) in aquatic mammals, transactivation potentials of the Baikal seal (Pusa sibirica) CAR (bsCAR) by environmental pollutants, including persistent organic pollutants (POPs) and brominated flame retardants (BFRs), were investigated using an in vitro reporter gene assay, and compared with those of the mouse CAR (mCAR). Measurement of luciferase reporter gene activities demonstrated that the seal CAR was activated by POPs, including a technical mixture of PCBs (Kanechlor-500), certain individual PCB congeners, DOT compounds, and trans-nonachlor. No or slight bsCAR-dependent activity was detected in experiments with PBDE congeners and HBCDs. The interspecies comparison of lowest observed effect concentration (LOEC) for CAR transactivation by each compound revealed that bsCAR responds more sensitively to PCBs than mCAR. In addition, bsCAR was weakly deactivated by PBDE99, whereas mCAR transcriptional activity decreased weakly by PBDE100, PBDE154, and PBDE187. Comparison of reporter gene activities by the congeners with the same IUPAC numbers among PCBs and PBDEs revealed that both bsCAR and mCAR were not activated by PBDE99 and PBDE153, but were activated by PCB99 and PCB153. The small ligand-binding pocket in CAR may contribute to difference in response between PCBs and PBDEs. Given that ethical rationale prevents dosing studies with such organohalogens in aquatic Mammals, Our in vitro assay system constructed with CAR cDNA from a species of interest provides a useful and realistic alternative approach in ecotoxicology.

DOI： 10.1021/es901120r

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

Here we report the inter-paralog comparison of cytochrome P4501A (CYP1A) catalytic function in common cormorant (Phalacrocorax carbo) using the recombinant proteins synthesized by yeast-based vector system. CYP1A4 and CYP1A5 proteins from common cormorant were heterologously expressed in yeast Saccaromyces cerevisiae. Kinetic analyses revealed that among alkoxyresorufin (methoxy-, ethoxy-, pentoxy- and benzyloxyresorufin) O-dealkylase (AROD) activities V(max) value for ethoxyresorufin O-deethylase (EROD) activity was the highest for both enzymes. reaching 0.91 +/- 0.034 and 1.8 +/- 0.043 nmol/min/nmol CYP for CYP1A4 and CYP1A5, respectively. Similar results were obtained for the catalytic efficiencies represented as the ratios of V(max) to K(m) (V(max)/K(m)). Meanwhile, distinct substrate preferences were also observed; CYP1A4 had V(max) and V(max)/K(m) values for benzyloxyresorufin O-debenzylase (BROD) activity 12- and 46-fold greater than CYP1A5, respectively, while CYP1A5 was about 13- and 4.5-fold more efficient in methoxyresorufin O-demethylase (MROD) activity than CYP1A4. The K(m) values showed no significant change among MROD, EROD, pentoxyresorufin O-depenthylase (PROD) and BROD activities for both enzymes, except for significant differences between PROD and other three activities for CYP1A4. Comparing the results in the present study with previous studies addressing chicken and rat CYP1A enzymes, it is also clear that CYP1A orthologs have different catalytic preferences for AROD activities between cormorant and rat and even between cormorant and chicken. Variations in CYP1A catalytic function between cormorant CYP1A paralogs and between CYP1A orthologs from cormorant and other species indicate that enzymatic properties should be characterized on the basis not only of a limited model species such as chicken, but also of multiple species to further understand the mechanism underlying differences in substrate selectivity and the interaction with environmental contaminants in avian species. (c) 2008 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.cbpc.2008.12.004

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

In this study we investigated the effect of a single-compound exposure or two compound co-exposure to tetrachlorodibenzo-p-dioxin (TCDD) plus perfluorooctane sulfonate (PFOS) OF perfluorooctanoic acid (PFOA) on the mRNA expression of cytochromes P450 (CYP) 1A4, 4V2 and 3A37, ethoxyresorufin-O-deethylase (EROD) activity and cell viability in chicken (Gallus gallus domesticus) embryo primary hepatocyte cultures. Cell viability after 24 h Of incubation was significantly decreased in cells exposed to PFOS at concentrations between 30 mu M and 60 mu M with or without co-exposure to TCDD (0.3 nM at maximum). PFOA did not decrease cell viability even at maximum concentrations of 60 mu M. TCDD induced CYP1A4 mRNA and EROD activity substantially as reported previously. PFOS also increased CYP1A4 mRNA in a concentration-dependent manner. Co-exposure of cells to PFOS plus TCDD did not change CYP1A4 mRNA levels compared to cells treated with TCDD alone. PFOS alone did not induce CYP4V2 mRNA, however 40-50 mu M PFOS Plus TCDD (0.3 nM) induced CYP4V2 mRNA compared to TCDD alone (P < 0.05). This trend was similar to that observed with cc-exposure to TCDD Plus PFOA, suggesting that PFOA alone did not induce CYP4V2 mRNA. whereas co-exposure to TCDD plus PFOA induced the expression levels. PFOS alone decreased CYP3A37 mRNA by a maximum of 45%. however after co-exposure to TCDD, recovery of mRNA expression to levels measured in DMSO-treated cells was observed. Our data Suggest a complex gene response to mixtures of dioxin-like and perfluorinated compounds. (c) 2009 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.cbpc.2009.01.001

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ACADEMIC PRESS INC ELSEVIER SCIENCE  

To elucidate the role of genetic factors in arsenic (As) metabolism, we studied associations of single nucleotide polymorph isms (SNPs) in As (+3 oxidation state) methyltransferase (AS3MT) with the As concentrations in hair and urine, and urinary As profile in residents in the Red River Delta, Vietnam. Concentrations of total As in groundwater were 0.7-502 mu g/l. Total As levels in groundwater drastically decreased by using sand filter, indicating that the filter could be effective to remove As from raw groundwater. Concentrations of inorganic As (IAs) in urine and total As in hair of males were higher than those of females. A significant positive correlation between monomethylarsonic acid (MMA)/IAs and age in females indicates that older females have higher methylation capacity from IAs to MMA. Body mass index negatively correlated with urinary As concentrations in males. Homozygote for SNPs 4602AA, 35991GG, and 37853GG, which showed strong linkage disequilibrium (LD), had higher percentage (%) of dimethylarsinic acid (DMA) in urine. SNPs; 4740 and 12590 had strong LD and associated with urinary %DMA. Although SNPs 6144, 12390, 14215, and 35587 comprised LD cluster, homozygotes in SNPs 12390GG and 35587CC had lower DMA/MMA in urine, suggesting low methylation capacity from MMA to DMA in homo types for these SNPs. SNPs 5913 and 8973 correlated with %MMA and %DMA, respectively. Heterozygote for SNP 14458TC had higher MMA/IAs in urine than TT homozygote, indicating that the heterozygote may have stronger methylation ability of IAs. To our knowledge, this is the first study on the association of genetic factors with As metabolism in Vietnamese. (C) 2009 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.taap.2009.01.015

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCI LTD  

This study investigated the accumulation features and temporal trends of PCDD/Fs, dioxin-like PCBs (DL-PCBs) and non-dioxin-like PCBs (NDL-PCBs) in the blubber of Baikal seals collected in 1992 and 2005. DL-PCBs (480-3600 ng/g) and NDL-PCBs (980-35,000 ng/g) were dominant contaminants. Concentrations of PCDDs and PCBs in males were significantly higher than in females. In males, age-dependent accumulation was observed for PCDDs, mono-ortho PCBs and NDL-PCBs. PCDFs and non-ortho PCBs showed no such trends, implying that exposure of seals to these contaminants has been decreasing in recent years. No decreasing temporal trend was observed for PCDDs, mono-ortho PCBs and NDL-PCBs, suggesting that Baikal seals are still exposed to PCDDs and PCBs. TEQs of PCDDs and mono-ortho PCBs in seals collected in 2005 accounted for 62-77% of total TEQs. The TEQ levels in 40% of the specimens exceeded the threshold level for immunosuppression observed in harbor seals (209 pg/g). (C) 2008 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.envpol.2008.11.027

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

Arsenic trioxide (ATO) is an effective therapeutic agent for acute promyelocytic leukemia (APL). In the present study, the concentrations of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and arsenic compounds [(dimethylarsinic acid (DMA), monomethylarsonic acid (MMA), As(V), and As(III)] in urine of an APL patient were determined during ATO treatment. The concentrations of 8-OHdG, DMA, and MMA were increased, especially during the fi rst consolidation therapy. Signifi cant positive correlations were observed between concentrations of 8-OHdG and DMA, between concentrations of 8-OHdG and MMA, and between concentrations of 8-OHdG and the sum of arsenic compounds. The present study supports the idea that urinary 8-OHdG can be a marker for arsenic poisoning, when it is detected together with DMA and MMA. In addition, this study is the fi rst to show the relationship between 8-OHdG and levels of arsenic compounds in urine of an APL patient being treated with ATO.

DOI： 10.1007/s11419-008-0062-x

Web of Science

Scopus

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCI LTD  

This study investigated the status of arsenic (As) exposure from groundwater and rice, and its methylation capacity in residents from the Red River Delta, Vietnam. Arsenic levels in groundwater ranged from <1.8 to 486 mu g/L Remarkably, 86% of groundwater samples exceeded WHO drinking water guideline of 10 mu g/L Also, estimated inorganic As intake from groundwater and rice were over Provisional Tolerable Weekly Intake (15 mu g/week/kg body wt.) by FAO/WHO for 92% of the residents examined. Inorganic As and its metabolite (monomethylarsonic acid and dimethylarsinic acid) concentrations in human urine were positively correlated with estimated inorganic As intake. These results suggest that residents in these areas are exposed to As through consumption of groundwater and rice, and potential health risk of As is of great concern for these people. Urinary concentration ratios of dimethylarsinic acid to monomethylarsonic acid in children were higher than those in adults, especially among men, indicating greater As methylation capacity in children. (C) 2008 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.envpol.2008.09.043

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Groundwater contamination by arsenic is a serious environmental problem in the world. Yet there have been few studies conducted in Southeast Asian countries. This article surveys arsenic contamination in groundwater and residents from Vietnam, and is based on our previous studies. Samples of groundwater (n = 118), human hair (n = 59), and urine (n = 100) were collected in the Red River and Mekong River Deltas during 2001-2004. Arsenic was detected in most of the groundwater samples, and its level ranged from &lt
0.1 to 486 μg/l. Elevated concentrations of arsenic were observed in groundwater at some locations in Ha Nam (up to 486 μg/l) in the Red River Delta and Dong Thap (up to 411 μg/l) in the Mekong River Delta. Remarkably, about 33% of these groundwater samples exceeded the WHO drinking water guideline of 10 μg/l. These results suggest that arsenic contamination in groundwater may be widely present in both the Red River and Mekong River Deltas, Vietnam. A significant positive correlation was observed between arsenic concentrations in groundwater and human hair. Arsenic speciation of human urine revealed the presence of inorganic arsenic, and these concentrations positively correlated with arsenic levels in groundwater. Thus, it is likely that residents in our study areas are chronically exposed to arsenic through drinking groundwater, suggesting that there is a health risk from arsenic in Vietnam.

DOI： 10.1080/00207230902759962

Scopus

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ACADEMIC PRESS INC ELSEVIER SCIENCE  

The present study focuses on the molecular mechanism and interspecies differences in susceptibility of avian aryl hydrocarbon receptor (AHR)-cytochrome P4501A (CYP1A) signaling pathway. By the cloning of 5′-flanking regions of CYP1A5 gene from common cormorant (Phalacrocorax carbo) and chicken (Gallus gallus), seven putative xenobiotic response elements (XREs) were identified within 2.7 kb upstream region of common cormorant CYP1A5 (ccCYP1A5), and six XREs were found within 0.9 kb of chicken CYP1A5 (ckCYP1A5). Analysis of sequential deletion and mutagenesis of the binding sites in avian CYP1A5 genes by in vitro reporter gene assays revealed that two XREs at -613 bp and -1585 bp in ccCYP1A5, and one XRE at -262 bp in ckCYP1A5 conferred TCDD-responsiveness. The binding of AHR1 with AHR nuclear translocator 1 (ARNT1) to the functional XRE in a TCDD-dependent manner was verified with gel shift assays, suggesting that avian CYP1A5 is induced by TCDD through AHR1/ARNT1 signaling pathway as well as mammalian CYP1A1 but through a distinct pathway from mammalian CYP1A2, an ortholog of the CYP1A5. TCDD-EC50 for the transcriptional activity in both cormorant AHR1- and AHR2-ccCYP1A5 reporter construct was 10-fold higher than that in chicken AHR1-ckCYP1A5 reporter construct. In contrast, chicken AHR2 showed no TCDD-dependent response. The TCDD-EC50 for CYP1A5 transactivation was altered by switching AHR1 between the two avian species, irrespective of the species from which the regulatory region of CYP1A5 gene originates. Therefore, the structural difference in AHR, not the CYP1A5 regulatory region may be a major factor to account for the dioxin susceptibility in avian species. © 2008 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.taap.2008.09.007

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

To assess the inducibility of avian metallothionein (MT) genes and potential tolerability of their protiens to element exposure, we investigated the transcriptional inducibilities of cormorant (Phalacrocorax carbo) and mallard (Anas platyrhynchos) MT genes in CV-1 cells by elements and detoxification potencies of their in vitro synthesized MT proteins. About 1.3 kb of 5'-upstream regions were sequenced for cormorant MT1 and 2 genes, where two metal-responsive elements were identified. Both cormorant MT promoters were dose dependently activated by Cd, Zn, Cu, and CH(3)Hg, whereas no transactivation was detected by Pb, Tl, Ag, inorganic Hg, Cr(VI), Cr(III), As(V), As(III), Ni, Co, Rb, and Bi, suggesting a shared transactivational mechanism of both MTs for specific elements. These findings support our previous results, where Cu and Zn concentrations were shown to be positively correlated with hepatic MT1/2 mRNA levels in wild cormorants. Comparison of EC(50) and LOEL (lowest observed effect level) for each element revealed that Cd was the most potent inducer of MT1/2 promoters, followed by CH3Hg, Zn, and Cu. Since LOELs of CH(3)Hg for both MT promoters were higher than the hepatic levels in wild cormorants, hepatic CH3Hg concentration may not be high enough to induce MT mRNA in the wild population. Although LOELs of Cd were much lower than the hepatic concentrations detected in wild cormorants, no significant correlation was observed between hepatic Cd levels and MT mRNAs. This may be due to the masking effect of multiple elements, probably by Zn and/or Cu that were highly accumulated in wild cormorants. Cotreatment of Cd with Zn supported a possible suppression of Cd-induced MT expression by Zn in wild cormorants. MT1 and 2 proteins of cormorant and mallard endowed Escherichia coli with significantly higher growth rate than control to Cd exposure (500-1000 mu M), implying that avian MTs could be involved in the detoxification of intracellular Cd. This study provides the first evidence on the inducibility of avian MT isoforms by specific elements and functional significance of each avian MT isoform in detoxifying intracellular heavy metals. Our in vitro approaches demonstrate their validity in predicting the response of MTs to element exposure in a wild avian population.

DOI： 10.1021/es801332p

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：SOC ENVIRONMENTAL TOXICOLOGY & CHEMISTRY-SETAC  

Contamination levels of perfluorinated compounds (PFCs), including perfluorooctanesulfonate (PFOS), perfluorononanoic acid (PFNA), perfluorooctane sulfonamide (PFOSA), perfluorohexanesulfonate (PFHS), and perfluorooctanoic acid (PFOA), were determined in the livers of wild common cormorants (Phalacrocorax carbo) from Lake Biwa, Japan. Potential effects of PFCs alone and combined effects by complex mixture of PFCs and dioxins and related compounds (DRCs) were also assessed by gene expression profiling using a cormorant oligo array. Perfluorooctanesulfonate, PFNA, and PFOSA were detected in almost all liver samples analyzed, while concentrations of PFHS and PFOA were below the limit of quantification. The microarray data analyses revealed that hepatic PFC levels were correlated with the expression of 74 genes. Real-time reverse-transcript polymerase chain reaction data demonstrated that PFOS concentration was positively correlated with mRNA levels of glutathione peroxidase 1 and glutathione S-transferase alpha 3 and negatively correlated with levels of heat shock 70-kDa protein 8 and tumor rejection antigen 1 mRNAs. These results suggest the induction of antioxidant enzymes in response to oxidative stress caused by PFCs and the suppression of molecular chaperones, leading to reduction in protein stability. Moreover, multiple regression analyses identified seven significant models in which certain genes showed expression levels altered by accumulation of PFCs and DRCs. The regression models explained associations with cytochrome P450 1A mRNA and protein expression levels, and its catalytic activity, ethoxyresorufin-O-deethylase of both PFNA and the 2,3,7,8-tetrachlorodibenzo-p-dioxin toxic equivalent levels. Thus, the regression models suggested the potential of PFCs to enhance toxicities of DRCs. Since mixture toxicity is an urgent issue, further study is required to understand the effects of mixtures of PFCs and DRCs in wild cormorants.

DOI： 10.1897/07-614.1

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCI LTD  

The present study clarifies the enzymatic properties of two avian cytochrome P4501A (CYP1A) paralogs, CYPIA4 and 1A5, using a yeast-based vector system. Recombinant CYP1A4 and 1A5 Proteins from common cormorant (Phalacrocorax carbo) were expressed in yeast cells, and showed typical reduced CO-difference spectra with a peak at 446 nm. Kinetic analysis of O-dealkylase of methoxy-, ethoxy-, pentoxy-and benzyloxyresorufin catalyzed by the CYP1A enzymes revealed that V-value for ethoxyresorufin-O-deethylase (EROD) activity was much higher than that for the other three O-dealkylase activities for both isozymes. Interestingly, remarkable substrate specificity of the CYP1As was observed for O-clealkylation of benzyloxyresorufin and methoxyresorufin; CYP1A4 was highly specific for catalyzing benzyloxyresorufin-O-debenzylase activity, whereas CYP1A5 was more efficient in catalyzing methoxyresorufin-O-demethylase activity. The present study also measured CYP1A-dependent EROD activity in the presence of 2,3,7,8-tetrachlorodibenzofuran (TCDF) to evaluate the ability of this dioxinlike congener to inhibit the EROD activity. One hundred nanomolar TCDF noncompetitively inhibited CYP1A5-dependent EROD activity, although no inhibitory effect was detected for CYPlA4-dependent EROD activity. These results indicate that the avian CYP1A paralogs have different affinities for substrate and inhibitor, thus suggesting their distinct physiological and toxicological roles. (C). 2008 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.marenvres.2008.02.047

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCI LTD  

Concentrations of total arsenic (As) and individual compounds were determined in green and hawksbill turtles from Ishigaki Island, Japan. In both species, total As concentrations were highest in muscle among the tissues. Arsenobetaine was a major compound in most tissues of both turtles. High concentrations of trimethylarsine oxide were (]elected in hawksbill turtles. A significant negative correlation between standard carapace length (SCL), an indicator of age, and total As levels in green turtles was found. In contrast, the levels increased with SCL of hawksbill turtles. Shifts in feeding habitats with growth may account for such a growth-dependent accumulation of As. Although concentrations of As in marine sponges, the major food of hawksbill turtles are not high compared to those in algae eaten by green turtles, As concentrations in hawksbill turtles were higher than those in green turtles, indicating that hawksbill turtles may have a specific accumulation mechanism for As. (C) 2007 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.envpol.2007.07.013

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

To investigate the biological effects of perfluorochemicals (PFCs) and to identify biomarkers of exposure to PFCs, this study focused on the effects mediated by peroxisome proliferator-activated receptor alpha (PPAR alpha) in Baikal seals (Pusa sibirica). We cloned a full-length cDNA encoding PPAR alpha from the liver of Baikal seal, which has a deduced open reading frame of 468-amino acid residues with a predicted molecular mass of 52.2 kDa. Comparison of the amino-acid sequence of Baikal seal PPAR alpha with that of other mammalian PPAR alpha showed considerable similarities with PPAR alpha of dog (97%), human (95%), rat (92%), and mouse (91%). The quantitative real-time RTPCR analyses of tissues from Baikal seals revealed that PPAR alpha mRNAs were primarily expressed in the liver, kidney, heart, and muscle. The hepatic expression levels of PPAR alpha mRNA showed a positive correlation with the expression levels of immunochemically detected cytochrome P450 (CYP) 4A-like protein, indicating that the PPAR alpha-CYP4A signaling pathway in Baikal seal is likely conserved. This study also developed an in vitro PPAR alpha reporter gene assay using African green monkey kidney CV-1 cells transiently transfected with Baikal seal PPAR alpha cDNA expression vector and a reporter vector containing a peroxisome proliferator-responsive element. The in vitro reporter gene assay displayed significant response to clofibrate, which is a known PPAR alpha agonist in humans and rodents. Treatment with perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), or perfluorooctane sulfonate (PFOS) induced PPAR alpha-mediated transcriptional activity in a dose-dependent manner, showing the lowest-observed-effect concentrations of 62.5, 125, 125, 62.5, and 125 mu M, respectively. In the livers of wild Baikal seals, expression levels of PPAR alpha mRNA showed a significant positive correlation with PFNA levels. Moreover, expression of hepatic CYP4A-like protein was significantly correlated with the hepatic concentrations of PFNA and PFDA. These results suggest modulation of the PPAR alpha-CYP4A signaling pathway by PFCs in the wild Baikal seals. Our study demonstrates that the PPAR alpha-mediated response may be a useful biomarker to evaluate potential biological effects of PFCs in wildlife.

DOI： 10.1021/es0720558

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

Concentrations of perfluorochemicals (PFCs) including perfluoroalkylsulfonates (PFSAs) and perfluoroalkylcarboxylates (PFCAs) were determined in liver and serum of Baikal seals (Pusa sibirica) collected from Lake Baikal, Russia in 2005. Among the 10 PFC compounds measured, perfluorononanoic acid (PFNA, 3.3-72 ng/g wet wt) concentrations were the highest in liver, followed by perfluorooctanesulfonate (PFOS, 2.6-38 ng/g). The accumulation profile of long-chain (C7-C12) PFCAs in particular, the predominance of PFNA, indicated that 8:2 fluorotelomer alcohol or commercially manufactured PFNA is a major local source of PFCs in Lake Baikal. No gender-related differences in the concentrations of individual PFCs or total PFCs were found. Tissues from pups and juveniles contained relatively higher concentrations of PFCs than tissues from subadults and adults, suggesting that maternal transfer of PFCs is of critical importance, Comparison of concentrations of PFCs in livers and sera collected from the same individuals of Baikal seals revealed that residue levels of PFOS, PFNA, perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA) were significantly higher in liver than in serum. The concentration ratios of PFNA and PFDA between liver and serum were calculated to be 14 and 15, respectively, whereas the ratio of PFOS was 2.4. This suggests preferential retention of both PFNA and PFDA in liver. Concentrations of PFOS, PFNA, and PFDA in liver were significantly correlated with those in serum, whereas concentrations of PFUnDA were not correlated in between the two tissues, suggesting differences in pharmacokinetics among these PFCs. Temporal comparisons of hepatic PFC concentrations in seals collected between 1992 and 2005 showed that the concentrations of PFOS (p = 0.0006), PFNA (p = 0.061) and PFDA (p = 0.017) were higher in animals collected in recent years, indicating ongoing sources of PFC contamination in Lake Baikal.

DOI： 10.1021/es072054f

Web of Science

Scopus

PubMed

researchmap

DOI： 10.11403/jset.11.117

researchmap

Language：English   Publishing type：Part of collection (book)   Publisher：SPRINGER  

Global contamination and toxic effects of persistent organic pollutants (POPs) have been an emerging environmental issue and have received considerable attention during the past four decades. Although the extent of contamination by POPs has been dominant in industrialized nations, an increasing number of recent investigations have highlighted the role of the Asia-Pacific region as a potential source of emission for these chemicals, particularly to pristine areas such as the Arctic and the Antarctic (Tanabe et al. 1994; Tanabe 2000, 2002; Tanabe and Subramanian 2006). © 2008 Springer.

DOI： 10.1007/978-0-387-73163-6_4

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

Concentrations of 19 trace elements (V, Cr, Mn, Fe, Co, Cu, Zn, Se, Rb, Sr, Mo, Ag, Cd, Sb, Cs, Ba, Tl, Hg, and Pb) were determined in the liver of the striped dolphins (Stenella coeruleoalba) collected around Japan during 1977-1982 to examine the sex difference, age dependence, and interrelationships among trace elements. Tissue distribution of trace elements was also investigated in one adult and one fetus specimens. Generally, concentrations of Se, Sr, Ag, Cd, Cs, Ba, Hg, and Pb were higher in the tissues of adult than those of fetus, whereas the opposite trend was observed for Cr and Tl. There were no significant sex differences in the trace element levels in the liver. Significant positive correlations between age (0-26.5 years) and hepatic concentrations were found for Ag, Se, Hg, V, Fe, Pb, and Sr, suggesting their age-dependent accumulation in the liver. In contrast, hepatic concentrations of Mn and Zn decreased with age. Significant positive relationships were observed between Se, and Hg, Ag, V, Fe, and Sr in the liver. (C) 2008 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.marpolbu1.2008.01.039

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

Total arsenic (As) and its compounds were determined in liver, kidney, muscle, and stomach contents of green turtles (Chelonia mydas). Total As concentrations in the muscle were higher than those in the kidney and liver. Arsenobetaine (AB) was the predominant compound in all the three tissues and its levels were positively correlated with total As concentrations. This indicates that AB greatly contributes to As accumulation in green turtles. Higher concentrations of remaining As in the sample after extraction were detected in the liver, implying that lipid-soluble or protein bound As compounds accumulate in the liver of green turtles. Total As levels in tissues showed significant negative correlations with standard carapace length. The size-dependence of As accumulation in green turtles may be related to their feeding habit, shifting from carnivore to herbivore at different growth stages. Concentrations of AB and dimethylarsinic acid (DMA) were low in the stomach contents but high in the tissues, implying bioaccumulation of these arsenicals in green turtles. (C) 2008 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.marpolbul.2008.01.010

Web of Science

Scopus

PubMed

researchmap

Language：Japanese  

DOI： 10.11403/jset.11.75

CiNii Books

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

Heavy oil contamination is one of the most important environmental issues. Toxicities of polycyclic aromatic hydrocarbons (PAHs), including immune toxicities, are well characterized, however, the immune toxic effects of heavy oil, as a complex mixture of PAHs, have not been investigated. In the present study, we selected Japanese flounder (Paralichthys olivaceus) as a model organism, and observed alteration of immune function by the exposure to heavy oil. To analyze the expression profiles of immune system-related genes, we selected 309 cDNAs from our flounder EST library, and spotted them on a glass slide. Using this cDNA array, alteration of gene expression profiles was analyzed in the kidneys of flounders exposed to heavy oil. Six Japanese flounders (mean body weight: 197 g) were acclimated to laboratory conditions at 19-20 degrees C. Three fish were exposed to heavy oil C (bunker C) at a concentration of 3.8 g/L for 3 days, and the others were kept in seawater without heavy oil and used as the control. After the exposure period, the fish were transferred into control seawater and maintained for 4 days, and then they were dissected and their kidneys were removed. Total RNA was extracted from the kidney samples to use in gene expression analyses. The microarray detected alteration of immune system-related genes in the kidneys of heavy oil-exposed flounders, including down-regulation of immunoglobulin light chain, CD45, major histocompatibility complex class II antigens and macrophage colony-stimulating factor precursor, and up-regulation of interleukin-8 and lysozyme. These results suggest that pathogen resistance may be weakened in heavy oil-exposed fish, causing a subsequent bacterial infection, and then proinflammatory genes may be induced as a defensive response against the infection. Additionally, we found candidate genes for use as biomarkers of heavy oil exposure, such as N-myc downstream regulated gene 1 and heat shock cognate 71 kDa proteins. (c) 2008 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.marpolbul.2008.02.021

Web of Science

Scopus

PubMed

researchmap

Language：English  

DOI： 10.11299/brte.19.265

CiNii Books

researchmap

Other Link： http://search.jamas.or.jp/link/ui/2009106807

Language：English  

DOI： 10.11299/brte.19.63

CiNii Books

researchmap

Other Link： http://search.jamas.or.jp/link/ui/2008358481

Language：English  

Proceedings

researchmap

This chapter provides an overview of the contamination by persistent organic pollutants (POPs) in Vietnam on the basis of the results of extensive monitoring studies conducted in our laboratory during the last two decades. Surveys conducted in the framework of Asia-Pacific Mussel Watch Program during early 1990s indicated widespread contamination by polychlorinated biphenyls (PCBs) and organochlorine (OC) insecticides, particularly DDTs and HCHs in various environmental compartments such as air, water, soils, sediments, and fish collected from different parts of Vietnam. Recent studies have revealed elevated contamination by DDTs in fish, mussels, and birds from Vietnam. Interestingly, DDT residue concentrations in fish and birds from Vietnam are among the highest values reported for the countries in Asia-Pacific region, suggesting the role of Vietnamese environment as a potential emission source of DDTs in this region. Open dumping sites for municipal wastes in some major cities such as Hanoi and Hochiminh City is a matter of concern with regard to environmental pollution, particularly contamination by dioxins (PCDDs) and related compounds such as dibenzofurans (PCDFs) and coplanar PCBs. Soils collected in dumping sites in Hanoi contained higher PCDD/F residues as compared to general soils collected far from dumping sites. PCDD/F concentrations in a few soil samples from Hanoi exceeded the environmental guideline values, suggesting potential health effects on humans and wildlife living near these dumping sites. Daily intakes of DDTs via seafood estimated for Vietnamese general population were among the highest values reported for East Asian countries. In the open dumping sites, intakes of dioxins by residents were significantly greater than those living far from dumping sites. Particularly, the estimated intakes of dioxins via soil ingestion and dermal exposure for children were higher than those for adults, suggesting greater risk of dioxin exposure for children in dumping sites. Future studies should be focused on the temporal trends of POPs in biota in Vietnam to predict the future trends of contamination and to understand possible toxic impacts on organisms. In addition, human exposure and possible toxic effects, particularly on children should be considered as priority research as they are the most susceptible group and have higher exposure levels to dioxins. © 2007 Elsevier Ltd. All rights reserved.

DOI： 10.1016/S1474-8177(07)07011-8

Scopus

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

Full-length cDNA sequences of cytochrome P450 (CYP) 2C78, 2EI, 3A72, 4A35 and 4V6 isozymes were isolated from a hepatic cDNA library of common minke whale (Balaenoptera acutorostrata). The deduced amino acid sequences of minke whale CYP2C78, 2131, 3A72, 4A35 and 4V6 showed high identities with cattle CYP2C86 (83%), pig CYP2E1 (85%), sheep CYP3A24 (82%), pig CYP4A21 (80%), and human CYP4V2 (76%), respectively. To investigate whether or not these CYP expression levels are altered by contamination of organochlorine contaminants (OCs), mRNA levels of these CYPs in the liver of common minke whale were measured using a quantitative real-time RT-PCR method, and the quantified mRNA levels were employed for the statistical analysis with the residue levels of OCs including PCBs, DDTs (p,p'-DDT, p,p-DDD and p,p'-DDE), chlordanes (cis-chlordane, trans-chlordane, cis-nonachlor, trans-nonachlor and oxychlordane), HCHs (alpha, beta- and gamma-isomers) and hexachlorobenzene that have already been reported elsewhere. Spearman's rank correlation analyses showed no significant correlation between CYP expression levels and each OC level in the common minke whale liver, implying that these environmental chemicals have no potential to alter the expression levels of these CYPs or the residue levels encountered in the whale livers may not reach their transcriptional regulation levels. This suggests that the expression of individual CYPs in the whale liver may be at basal level. Relationships among hepatic mRNA expression levels of these CYP2-4 isozymes together with CYP1A1 and CYP1A2 were also examined. Significant positive correlations were detected among mRNA expression levels of individual CYP isozymes in most cases. These associations indicate that the transcriptional regulation of these CYPs examined in this study maybe reciprocally related. CYP1A1 levels showed a positive correlation with CYP1A2 levels (r=0.64,p < 0.01) indicating that both CYP isozymes were regulated by aryl hydrocarbon receptor activated by endogenous ligands. A strong positive correlation between CYP2C78 and 3A72 (r=0.90, p < 0.001) suggests that expression of these CYP isozyrnes may be under a regulation mechanism of cross-talk in which specific nuclear receptors such as constitutive androstane receptor and pregnane X receptor are involved. The present study indicates that minke whale from the North Pacific may be a model species to investigate the mechanism of basal regulation of these CYPs. (c) 2007 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.cbpb.2007.04.005

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

Tributyltin (TBT) is organotin compound that is toxic to aquatic life ranging from bacteria to mammals. This study examined the concentration of TBT in sediment from and near the Mekong River and the distribution of TBT-resistant bacteria. TBT concentrations ranged from <2.4 to 2.4 ng/g (dry wt) in river sediment and <2.4-15 ng g(-1) (dry wt) in harbor sediment. Viable count of total bacteria ranged from 2.0 x 10(4) to 1.4 x 10(7) cfu/g, and counts of TBT-resistant bacteria ranged <1.0 x 10(2) to 2.5 x 10(4) cfu/g. The estimated occurrence rate of TBT-resistant bacteria ranged from <0.01 to 34% and was highest in upstream sites in Cambodia. The occurrences of TBT in the sediment and of TBT-resistant bacteria were unrelated, and chemicals other than TBT might induce TBT resistance. TBT-resistant bacteria were more abundant in the dry season than in the rainy season. Differences in the selection process of TBT-resistant bacteria between dry and rainy seasons were examined using an advection-diffusion model of a suspended solid (SS) that conveys chemicals. The estimated dilution-diffusion time over a distance of 120 km downstream from a release site was 20 days during dry season and 5 days during rainy season, suggesting that bacteria at the sediment surface could be exposed to SS for longer periods during dry season. (C) 2007 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.chemosphere.2007.03.033

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Oxford University Press (OUP)  

DOI： 10.1093/toxsci/kfm139

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：OXFORD UNIV PRESS  

This study attempts to relate the 2,3,7,8-tetrachlorodibenzo-p-dioxin toxic equivalent (TEQ) level with certain responses including the catalytic activities and expression of hepatic cytochrome P450 (CYP) 1A and CYP1B in wild population of Baikal seal (Pusa sibirica). We isolated full-length CYP1A1, 1A2, and 1B1 cDNAs, which encode proteins of 516, 512, and 543 amino acids, respectively. Immunochemical analysis demonstrated that a cross-reactive protein with polyclonal antibody against rat CYP1A1 or CYP1B1 was detected in the seal liver. Total TEQ levels showed significant positive correlations with expression levels of CYP1A1, 1A2, and 1B1 mRNAs, and further with both CYP1A- and CYP1B-like proteins, indicating chronic induction of these CYP isozymes by TEQs. The 50% effective concentration for CYP1A-like protein induction was estimated to be 65 pg TEQ/g wet weight. To evaluate the potential of congener-specific metabolism, profiles of negative correlations between the concentrations of eachcongener normalized to a relatively recalcitrant congener, PCB169, and CYP1A-like protein levels were also estimated. Significant negative correlations of 2,3,7,8-tetrachlorodibenzofuran and PCB77 to CYP1A-like protein expression may possibly be due to the preferential metabolism of these congeners. Anti-rat CYP1A1 and CYP1B1 antisera equivalently inhibited ethoxyresorufin O-deethylase (EROD) activity in the seal microsomes, suggesting that both CYPs are involved in EROD activity. Hepatic EROD revealed an increasing trend at lower TEQs, but a declining trend at higher levels, implying a catalytic inhibition of CYP1A and CYP1B. Furthermore, ratios of CYP1B1/CYP1A1 mRNA expression levels increased with TEQs, indicating the enhanced risk of carcinogenicity by preferential induction of CYP1B1 by TEQs in the liver.

DOI： 10.1093/toxsci/kfm066

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

High concentration of mercury (Hg) in hair has been reported for Cambodians. To confirm the Hg contamination occurring through intake, Hg concentrations were determined in both hair and blood of residents (n = 20) from Phnom Penh, Cambodia. Mercury concentrations in the hair and blood were 0.69-190 mu g g(-1) dry wt and 5.2-58 mu g l(-1), respectively, which were lower than those from Hg contaminated or high fish intake regions, but were higher than those from non-contaminated regions. Some female subjects had hair and blood Hg levels exceeding the threshold values for neurotoxic effects. Interestingly, serum estrone and estradiol levels were positively correlated with blood Hg level for both males and females, indicating possible induction of female hormones by Hg exposure in Cambodians. (c) 2007 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.chemosphere.2007.01.003

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE BV  

To stimate the influence of water contaminants on fish reproduction in the Mekong Delta area, we sampled cultivated male catfish (Pangasianodon hypophthalmus), investigated testicular development, and measured persistent organic pollutants (POPs) and trace element levels in muscle and liver, respectively. Various testes sizes were observed although sampling took place during a short period. Histological analysis revealed that all developmental stages of germ cells were observed in catfish with large testis, whereas only necrotic spermatogonia but no other germ cells were observed in catfish with small testis. In small testis, furthermore, vacuolization and hypertrophy of Sertoli cells were observed. Measurement of POPs in muscle and trace elements in liver demonstrated that there were negative correlations between GSI and the concentrations of Pb, Mo, Rb and As. To clarify possible direct effects of Pb, Mo, Rb and As on spermatogenesis in fish, we investigated the effects of these trace elements on spermatogenesis using in vitro testicular organ culture of Japanese eel (Anguilla japonica). Treatment with each of the trace elements alone did not affect spermatogenesis. However, treatment with 10(-7) M of Pb, 10(-5) and 10(-4) M of Mo, 10(-5) -10(-3) M of Rb or 10(-5) M of As inhibited the spermatogenesis induced by 11-ketotestosterone (11 KT). Furthermore, treatment with 10(-4) M of As in combination with 11KT caused necrosis of testicular fragments. Taken together, these results are consistent with the hypothesis that Ph, Mo, Rb and As can exert inhibitory effects on spermatogenesis in catfish inhabiting the Mekong Delta area. (C) 2007 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.aquatox.2007.03.010

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

Surficial sediment samples were collected from Hochiminh City canals, the Sai Gon-Dong Nai River, and its estuary, one of the most predominant industrial areas in Hochiminh City, southern Vietnam, for determination of selected persistent organic pollutants (POPs). Contamination pattern was as follows: PCBs >= DDTs > HCB > CHLs > HCHs. Concentrations of PCBs and DDTs ranged from 0.50-150 ng/g and 0.15-72 ng/g dry wt, respectively. On the other hand, concentrations of CHLs, HCHs, and HCB were mostly < 2 ng/g dry wt. Levels of the all organochlorines (OCs) in Hochiminh City canals were significantly higher than those in the other areas, indicating the urban areas as major pollution sources to the aquatic environment. The contamination pattern was PCBs > DDTs in the city canals but PCBs < DDTs in the downstream and the estuary, suggesting particularly high contamination by PCBs in the city. Examination of DDTs composition and their ratios demonstrated continuous input of this pesticide to the city canals. However, the combination of our data and those from available literature implies a decreasing trend of PCBs and DDTs in the environment. DDTs concentrations have been reduced 50% after approximately 5 years. Composition of CHLs in the sediment from Hochiminh City canals was comparable to those of common technical mixtures, suggesting continuous input of CHLs to the environment. CHLs might be in use for purposes like termite control, wood preservation, and protection of underground cables. Hazard assessment implies high toxic potential of DDTs for sediments from Hochiminh City canals and suggests the need for better management of municipal discharges.

DOI： 10.1007/s00244-006-0157-5

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

High levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related planar halogenated aromatic hydrocarbons (PHAHs) are accumulated in fish-eating birds including common cormorant (Phalacrocorax carbo). Most of the biochemical and toxic effects of TCDD are mediated by a basic helix-loop-helix and a conserved region among Per, ARNT, and Sim (bHLH/PAS) proteins, aryl hydrocarbon receptor (AHR) and AHR nuclear translocator (ARNT). To study the molecular mechanism of TCDD toxicity in common cormorant as an avian model species, characterization of the AHR/ARNT signaling pathway in this species is necessary. The present study focuses on molecular characterization of ARNT from common cormorant (ccARNT). The cDNA of the ccARNT isoform, ccARNT1 obtained by the screening of hepatic cDNA library contains a 2424-bp open reading frame that encodes 807 amino acids, exhibiting high identities (92%) with chicken ARNT. This isoform contains a unique 22 amino acid residue in 3' end of PAS A domain as is also recognized in chicken ARNT. The ccARNT2 cDNA isolated from brain tissue has a 2424-bp open reading frame. The deduced amino acid sequence of ccARNT2 protein (716 aa) shows a conservation of bHLH and PAS motif in its N-terminal region with high similarities (96% and 78%, respectively) to that of ccARNT1. Using quantitative RT-PCR methods, the tissue distribution profiles of ccARNT1 and ccARNT2 were unveiled. Both ccARNT1 and ccARNT2 mRNAs were ubiquitously expressed in all examined tissues including liver. The expression profile of ccARNT1 was comparable with that of rodent ARNT1, but ccARNT2 was not with rodent ARNT2, implying different roles of ARNT2 between the two species. There was a significant positive correlation between ARNT1 and ARNT2 mRNA expression levels in the liver of wild cormorant population, indicating that their expressions may be enforced by similar transcriptional regulation mechanism. Novel variants of ccARNT1 and ccARNT2 isoforms that were supposed to arise from their splicing process were also identified and their hepatic expression profiles were determined. These results indicate that ccARNT1, ccARNT2 and their splice variants may more intricately regulate the AHR/ARNT signaling pathway and consequently may be responsible for the species diversity of toxic effects and susceptibility to PHAHs. (c) 2007 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.cbpc.2007.01.007

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

The Mekong River delta is one of the largest agricultural land in the Southeast Asia. It plays a very important role for agriculture and fisheries in South Vietnam. However, comprehensive studies on the environmental pollution of persistent organic pollutants (POPs) in Mekong River delta have not been carried out in recent years. In this study, we collected sediment samples from the Mekong River to evaluate the contamination and ecological risks caused by several POP's. The contamination pattern of POPs was DDT > PCBs > CHLs > HCHs > HCB. DDTs are the most abundant pollutants, their concentration ranging from 0.01 to 110 ng/g dry wt, followed by PCBs (0.039-9.2 ng/g dry wt). DDTs and PCBs concentrations were higher in sediment from adjacent to urban areas than those from rural and agricultural sites, suggesting urban areas as important point sources of DDTs and PCBs to the river. Ratio of pp'-DDT/p,p'-DDE was lower compared to those previously reported. However, some samples still had the ratio higher than 0.5, indicating recent input of DDT into the aquatic environments. This result shows that although the magnitude of contamination decreased over time, recent inputs of DDTs to the river still occur. Some sediment samples had concentrations of DDT compounds higher than the standards from the Canadian Environmental Quality Guideline, suggesting continuous monitoring for POPs contamination in the Mekong River is necessary. (c) 2006 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.chemosphere.2006.05.144

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：BLACKWELL PUBLISHING  

Recently, a serious disease spread extensively in aquaculture sites of the ascidian Halocynthia roretzi in Korea. To understand circumstances of ascidians in Korean aquaculture sites, residue levels of organotin compounds were analyzed, and detection of a marine birnavirus (MABV) in tissues of H. roretzi was attempted. Korean H. roretzi showed high concentrations of butyltins (mono, di, and tributyltins), especially in the gill, hepatopancreas, and digestive tract. However, there was no significant difference in the residues of butyltins in the hepatopancreas between diseased and non-diseased ascidians. The positive rate of MABV detection was high in the hepatopancreas, but also no significant difference was observed between diseased and non-diseased individuals. These observations suggest that an accumulation of tributyltin and a latency of MABV in H. roretzi tissues does not directly relate to the occurrence of the disease.

DOI： 10.1111/j.1444-2906.2007.01332.x

Web of Science

Scopus

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

To characterize avian MTs, MT cDNAs were cloned from liver of cormorant (Phalacrocorax carbo) and mallard (Anas platyrhynchos). Expression profiles of NIT isoforms and relationships between metal accumulation and MT mRNA expression in tissues were also investigated. We succeeded in cDNA cloning of MT1/2 from cormorant and MT1 in mallard. DNA sequence of chicken MT1 was obtained from chicken (Gallus gallus) genomic database. Considering previous reports on avian MTs, birds possess at least two distinct MT isoforms. Comparison of genomic synteny among vertebrates and phylogenetic analysis of MT amino acid sequences revealed that avian MT 1/2 are evolutionarily close to mammalian MT3. Messenger RNAs of both MT isoforms were detected in all the tissues/organs in cormorant and mallard. Liver was the primary organ for cormorant MT1/2, and mallard MT2, whereas MT1 was dominant in mallard heart. Interspecies comparison of tissue distribution of MT mRNA expression between cormorant and mallard indicated that MT2 profile was similar, but MT1 was not. Significant positive correlations of mRNA expression levels between MT1 and MT2 were observed in the liver and kidney of cormorants, whereas no correlation was found in mallards. Expression levels of cormorant MT1/2 showed significant positive correlations with hepatic Cu and Zn concentrations, suggesting that both MT isoforms were induced by Cu and Zn in livers. Cormorant MT2 expression level exhibited a significant positive correlation with hepatic Ag, and a negative correlation with Rb, indicating that Ag and Rb concentrations depend on the expression of MT2 by Cu and Zn. In mallard, MT1 had no correlation with any metal concentration, and MT2 expression was positively correlated only with Cu, even though hepatic Cu and Zn concentrations in mallard were much higher than in cormorant. This may indicate that cormorant is a more susceptible species than mallard in terms of MT induction. These findings suggest tissue-, species-, and MT isoform-specific responses to metal stresses in these aquatic birds. (c) 2007 Elsevier Inc. All tights reserved.

DOI： 10.1016/j.cbpc.2006.10.012

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCI LTD  

Concentrations of 20 trace elements were determined in muscle and liver of 34 species of marine fish collected from coastal areas of Cambodia, Indonesia, Malaysia and Thailand. Large regional difference was observed in the levels of trace elements in liver of one fish family (Carangidae): the highest mean concentration was observed in fish from the Malaysian coastal waters for V, Cr, Zn, Pb and Bi and those from the Java Sea side of Indonesia for Sn and Hg. To assess the health risk to the Southeast Asian populations from consumption of fish, intake rates of trace elements were estimated. Some marine fish showed Hg levels higher than the guideline values by U.S. Environmental Protection Agency and Joint FAO/WHO Expert Committee on Food Additives (JECFA). This suggests that consumption of these fish may be hazardous to the people. (c) 2006 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.envpol.2006.04.034

Web of Science

Scopus

PubMed

researchmap

researchmap

researchmap

Language：Japanese   Publisher：PHARMACEUTICAL SOC JAPAN  

The 21st Century's Center of Excellence (COE) Program "Coastal Marine Environmental Research" in Ehime University, funded by the Ministry of Education, Culture, Sports, Science and Technology, Government of Japan, started its activities in October 2002. One of the core projects of the COE Program in Ehime University is "studies on environmental behavior of hazardous chemicals and their toxic effects on wildlife". This core project deals with studies of the local and global distribution of environmental contaminants in aquatic ecosystems, retrospective analysis of such chemicals, their toxicokinetics in humans and wildlife, molecular mechanisms to determine species-specific reactions, and sensitivity of chemically induced effects, and with the development of methodology for risk assessment for the conservation of ecological and species diversity. This presentation describes our recent achievements of this project, including research on contamination by arsenic and organohalogen pollutants in the Mekong River basin and molecular mechanisms of morphologic deformities in dioxin-exposed red seabream (Pagrus major) embryos. We established the Environmental Specimen Bank (es-BANK) in Ehime University in 2004, archiving approximately 100000 cryogenic samples containing tissues of wildlife and humans that have been collected for the past 40 years. The CMES homepage offers details of samples through online database retrieval. The es-BANK facility was in operation by the end of 2005.

DOI： 10.1248/yakushi.127.417

Web of Science

Scopus

PubMed

researchmap

researchmap

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE BV  

The toxicity of dioxins such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is mainly mediated by the aryl hydrocarbon receptor (AHR), which regulates the multiple target genes including cytochrome P4501A (CYP1A). In general, bony fishes, which possess at least two distinct AHRs are one of the most sensitive vertebrates to TCDD in early life stage. However, the physiological and toxicological roles of piscine multiple AHRs are not fully understood, especially in marine fish. To understand which AHR is responsible for TCDD toxicity in a marine fish species, we characterized the early life stage toxicity related to the expression of AHRs and CYP1A in red seabream (Pagrus major). The embryos at 10 h post-fertilization (hpf) were treated with 0-100 mu g/L TCDD for 80 min waterborne exposure. TCDD dose-dependently elicited developmental toxicities including mortality, yolk sac edema, retarded body growth, spinal deformity, reduced heart rate, shortened snout, underdeveloped fin, heart, and lower jaw. Intriguingly, hemorrage and pericardium edema, typical TCDD developmental defects noticed in other fish species, were not found in red seabream until test termination. The ECegg 50s for yolk sac edema, underdeveloped fin, and spinal deformity were 170, 240, and 340 pg/g, respectively. The LC(egg)50 was 360pg/g embryo, indicating that this species is one of the most sensitive fishes to TCDD toxicity. The expression levels of rsAHR1, rsAHR2 and CYP1A mRNAs were also determined in different developmental stages. The rsAHR2 mRNA expression dose-dependently increased following TCDD exposure, while rsAHR1 mRNA level was not altered. Level of rsAHR2 mRNA measured by two-step real-time PCR was 30 times higher than rsAHR1 in embryos treated with the highest dose. Temporal patterns of rsAHR2 and CYP1A mRNAs were similar in TCDD-treated embryos, representing a significant positive correlation between rsAHR2 and CYP1A mRNA levels, but not between rsAHR1 and CYP1A. In comparison of temporal trends of TCDD-induced AHRs and CYP1A expression, and developmental toxicities, the highest expression of rsAHR2 and CYP1A mRNA were detected prior to the appearance of maximal incidence of TCDD toxic manifestations. These results suggest that rsAHR2 may be dominantly involved in the transcriptional regulation of CYP1A, and several TCDD defects are dependent on the alteration of rsAHR2 and/or rsAHR2-CYP1A signaling pathway that is controlled through their expression levels. (c) 2006 Published by Elsevier B.V.

DOI： 10.1016/j.aquatox.2006.08.006

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：OXFORD UNIV PRESS  

To characterize the function of constitutive active/androstane receptor (CAR) in aquatic mammals, CAR complementary DNA (cDNA) was cloned from the liver of Baikal seal (Pusa sibirica) from Lake Baikal, Russia, and the messenger RNA (mRNA) expression levels in various tissues/organs of the wild population and the CAR ligand profiles were investigated. The seal CAR cDNA had an open reading frame of 1047 bp encoding 348 amino acids that revealed 74-84% amino acid identities with CARs from rodents and human. The mRNA expression profile of tissues/organs represented that Baikal seal CAR was predominantly expressed in the liver followed by heart and intestine. The expression analysis of hepatic CAR mRNA showed no correlation with expression of cytochrome P450 (CYP) 1A, 1B, 2B, 2C, and 3A-like proteins, indicating that the CAR expression level may not be the sole determinant of the regulation of these CYP expressions in the seal liver. There was no significant correlation between CAR expression and any of the persistent organic pollutants (POPs) levels. Furthermore, we performed an in vitro CAR transactivation assay using MCF-7 cells transfected with Baikal seal CAR expression plasmid and (NR1)(3)-luciferase reporter gene plasmid. In the transactivation analysis of Baikal seal CAR, neither repression by androstanol and androstenol, nor activation by estrone and estradiol, which are recognized as endogenous ligands for mouse and human CARs, was detected. On the other hand, bile acids such as chenodeoxycholic acid, deoxycholic acid, and lithocholic acid activated the seal CAR as well as mouse CAR. As for exogenous chemicals, the seal CAR was transactivated by a human CAR agonist, 6-(4-chlorophenyl)imidazo[2,1-b][1,3]thiazole-5-carbaldehyde O-(3,4-dichlorobenzyl)oxime), but not by a mouse CAR agonist, (1,4-bis[2-(3,5-dichloropyridyloxy)]benzene). In addition, the seal CAR was also activated by polychlorinated biphenyls (PCBs) (Kanechlor-500, International Union of Pure and Applied Chemistry No. PCB153; 2,2',4,4',5,5'-hexachlorobiphenyl and PCB180; 2,2',3,4,4',5,5'-heptachlorobiphenyl), and 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (p,p'-DDT) and its metabolite, 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE). The seal CAR responded more sensitively to PCBs than the mouse CAR. Based on the results of CAR transactivation assay, the lowest observable effect levels of Kanechlor-500, PCB153, PCB180, p,p'-DDT, and p,p'-DDE in Baikal seal were estimated to be 10, 20, 20, 10, and 10 ppm on wet weight basis, respectively. These results suggest that CAR is conserved in diverse mammalian species including seals. Whereas the seal CAR-mediated gene transcription may potentially be a sensitive response to the exposure of certain POPs, the ligand profile of seal CAR may be different from those of other mammalian CARs. This study indicates that CAR-mediated responses may be useful information to assess the ecotoxicological risk of xenobiotics such as POPs in wildlife but the previous results derived from rodent and human CAR may not be applicable to the risk assessment in wild species.

DOI： 10.1093/toxsci/kfl088

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

Commercial feeds for aquaculture and catfish samples were collected from the Mekong River Delta, Vietnam, for determination of polybrominated diphenyl ethers (PBDEs) and selected persistent organochlorines, including polychlorinated bi-phenyls (PCBs), DDT and its metabolites (DDTs), chlordane-related compounds (CHLs), hexachlorocyclohexane isomers (HCHs), and hexachlorobenzene (HCB). The most abundant contaminants were DDTs, with concentrations ranging from 10 to 700 ng/g lipid weight, followed by PCBs (1.0-80 ng/g), CHLs (< 0.01-8.2 ng/g), PBDEs (0.12-3.7 ng/g), HCHs (< 0.03-5.1 ng/g), and HCB (< 0.07-3.2 ng/g). Polybrominated diphenyl ethers were detected in all samples, suggesting their widespread contamination in the region. However, PBDE contamination levels in the present catfish specimens were low in comparison to levels worldwide. Interestingly, residue levels of all the contaminants were significantly higher in catfish collected near a municipal dumping site compared to farmed catfish. This suggests that runoffs from the dumping site during floods and rains may have brought pollutants to the surrounding areas. Contamination pattern in aquaculture feeds revealed elevated levels of PCBs and PBDEs in samples from foreign companies, perhaps implying their higher residues in some imported ingredients. Congener profiles of PBDEs and PCBs demonstrated similarity between the farmed catfish and the aquaculture feeds, suggesting these feeds as a major source of pollution to the farmed catfish. On the other hand, the PBDE and PCB profiles in the dumpsite catfish are clearly different from those of the farmed catfish, revealing their exposure to different sources. Risk assessment showed significantly higher intake of the contaminants by people who eat catfish cultured near the dumping areas. Further investigation regarding fate and occurrence of the contaminants in dumping sites is necessary.

DOI： 10.1897/05-600R.1

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

Concentrations of persistent organochlorines (OCs)-such as polychlorinated biphenyls (PCBs), 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) and its metabolites (DDTs), hexachlorocyclohexane isomers (HCHs), chlordane compounds (CHLs), hexachlorobenzene, and tris(4-chlorophenyl)methane [TCPMe]-were determined in plasma samples from residents of three sub-metropolitan locations in Japan (Miyako, Saku, and Tottori) for the purpose of studying the geographic variation and specific accumulation of OCs. Residue concentrations of PCBs and DDTs were the highest in samples collected in Saku (400 and 370 ng/g lipid wt, respectively) whereas samples from Miyako contained greater CHL residues (70 ng/g lipid wt) than those from the other two locations. This contamination pattern reflects the historic use of OCs in each area. For the first time, tris (4-chlorophenyl) methane (TCPMe) concentrations were detected in most of the plasma sample analyzed. Concentrations of TCPMe which ranged from < 0.1 to 8.1 ng/g lipid wt eight, were lower than those previouly reported in other human tissue. Larger geographic differences in OC accumulation were observed for PCBs and CHLs, whereas DDTs and HCHs exhibited little variability. PCB concentrations in samples from Saku residents were higher than those from residents of countries in the circumpolar Arctic region but lower than those reported for some populations in the United States and Western European countries. Interestingly, CHL residue concentrations in human blood from Japan are among the highest values reported for the countries examined, suggesting continued increased exposure to CHLs of the Japanese population. Time-trend analysis of CHLs in human blood samples from Miyako (Okinawa prefecture) showed that CHL residues have decreased substantially during the last decade, indicating the effect of the official ban of CHLs in 1986 in Japan. Isomer-specific analysis of PCBs revealed lower proportions of higher chlorinated congeners such as hepta- and octachlorobiphenyls in women than in men, suggesting the possibility of preferential elimination of higher chlorinated biphenyls in women. The difference in sex-dependent accumulation of OC compounds in healthy and ill persons was suggested. To our knowledge, this is the first report on the specific accumulation of persistent QCs, including TCPMe, in human blood samples from Japan.

DOI： 10.1007/s00244-004-0251-5

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：OXFORD UNIV PRESS  

The present study characterized cytochrome P4501A (CYP1A) isoforms from common cormorant (Phalacrocorax carbo) with regard to their evolutionary relationships and their roles in disposition of dioxin and related compounds (DRCs). Two clones isolated from a cormorant liver cDNA library were named CYP1A4 and CYP1A5 on the basis of greatest overall amino acid identity shared with chicken (Gallus gallus) CYP1A4 (78%) and CYP1A5 (78%), respectively. Spatial heterogeneity in phylogenetic signal along the sequences strongly indicated that cormorant CYP1A4 and CYP1A5 have undergone partial interparalog gene conversion, similar to chicken and mammalian CYP1As. Phylogenetic analysis of a putatively unconverted region produced a tree topology consistent with the orthology of avian CYP1A5s with mammalian CYP1A2s and avian CYP1A4s with mammalian CYP1A1s. Hepatic CYP1A4 and CYP1A5 mRNA levels in wild cormorants from Lake Biwa, Japan, were quantified to examine the effects of DRCs on isoform-specific expression and to evaluate the toxicokinetics of DRCs in which CYP1A expression is involved. Both CYP1A4 and CYP1A5 mRNA levels were positively correlated with total tetrachlorodibenzo-p-dioxin toxic equivalents and concentrations of each congener in most cases in the liver, suggesting the induction of both enzymes through a shared transcriptional mechanism. The lack of correlation of 2,3,7,8-tetrachlorodibenzofuran and 3,3',4,4'-tetrachlorobiphenyl (PCB77) to CYP1A gene expression is likely due to the rapid metabolism of these two congeners. Liver-to-muscle concentration ratios for most DRC congeners except PCB77 and mono-ortho coplanar polychlorinated biphenyls significantly increased with an elevation of CYP1A4 and CYP1A5 mRNA levels. The present data suggest that hepatic sequestration of some DRCs occurs in cormorant via binding to either CYP1A5 or both CYP1A4 and CYP1A5.

DOI： 10.1093/toxsci/kfl001

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

In Asian developing countries, large amounts of municipal wastes are dumped daily in open dumping sites without proper management. This practice may cause several adverse environmental consequences and increased health risk to local communities. To elucidate contamination by persistent organic pollutants (POPs)-including dichloro-diphenyl-trichloroethane and its metabolites (DDTs), hexachlorocyclohexanes (HCHs), chlordanes, hexachlorobenzene (HCB), and polychlorinated biphenyls (PCBs)-in such dumping sites, soil samples were collected from open dumping sites and respective control sites in Cambodia, India, and Vietnam from 1999 through 2001. Our results demonstrated that DDTs, PCBs, and HCHs were dominant contaminants in the dumping sites. However, the contamination pattern was not consistent, showing higher HCHs in India than in Cambodia and Vietnam. Interestingly, in all of the countries, extremely higher levels of POPs were observed in the dumping sites compared with those in the respective control sites, suggesting significant amplification of POP contamination in the dumping sites of Asian developing countries. Mean concentrations of DDTs and PCBs were 350 and 140 ng/g dry weight, respectively, in the dumping sites of Cambodia and 26 and 210 ng/g, respectively, in India. These residue levels were hundreds to thousands times higher than those in general soils, implying possible risk to human health of the local communities, especially to the rag pickers, including children who work in these sites to collect recyclable materials. Composition of DDT compounds suggested their recent use in populated areas, which in turn might have caused increased levels of DDTs in the open dumping sites. In addition, composition of HCH isomers revealed their different use pattern in different countries.

DOI： 10.1007/s00244-005-1087-3

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：SETAC  

Concentrations of dioxins and related compounds (DRCs), such as polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and coplanar polychlorinated bipherryls (Co-PCBs), were determined in black-eared kites (BEKs; Milvus migrans) collected from the Kanto district in Japan. Total 2,3,7,8-tetra-CDD toxic equivalents (TEQs) were in the range of 99 to 3,800 pg/g lipid weight in the liver and 42 to 760 pg/g lipid weight in the pectoral muscle. Three congeners, including PCB 126, 2,3,4,7,8-penta-CDF, and 1,2,3,7,8-penta-CDD, made a greater contribution to total TEQs in both tissues. Levels of ethoxyresorufi n-O-deethy lase activity and a cross-reactive protein with anti-rat cytochrome P4501 A (CYPIA) polyclonal antibodies showed no significant correlation with hepatic TEQs. This may be attributed to low sensitivity and insufficient TEQ levels to cause CYPIA induction, high metabolic potential of a series of congeners, and influence of CYPIA inducers other than DRCs. Most of the PCDD/ Fs and non-ortho Co-PCBs exhibited a total TEQ- and CYPIA-dependent increase in the liver to muscle concentration ratios, implying their concentration-dependent hepatic sequestration in which CYPIA was involved. Comparison of the toxicokinetics in avian species revealed that BEKs possibly have higher potentials than common cormorants for metabolizing and sequestering certain congeners in the liver in terms of hepatic concentration profiles and liver:muscle concentration ratios, respectively. These results clearly indicate that the toxicokinetics of DRCs is congener-, tissue-, and species-specific as well as concentration-dependent. Therefore, CYPIA expression is one of the critical factors that determine the toxicokinetics in wild avian species.

DOI： 10.1897/05-224R.1

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCI LTD  

The present study determined the contamination levels and congener-specific accumulation features of dioxins and related compounds (DRCs) in wild terrestrial mammals such as large Japanese field mice (LJFM), lesser Japanese moles (LJMs), and raccoon dogs (RDs) collected from Kanto region in Japan during 2001. The toxic equivalent quantity (TEQ) levels in the carcasses or adipose tissues were in the order of RDs >= LJMs > LJFM. Comparison of DRC congener profiles in the three species and principal component analysis (PCA) demonstrated a higher contribution of OCIDD, T(4)CB77, and P(5)CB118 in LJMs. Analysis of liver-adipose distribution of DRC congeners in RDs showed that livers contained significantly higher TEQs than adipose tissues, indicating that liver is a depository organ and critical for determining the toxicokinetics of DRCs. As for most T-4, P-5, H6CDD/DFs and for P(5)CB126, H(6)CB169 and mono-ortho PCB congeners, their liver/adipose concentration ratios in RDs revealed a tendency to increase with hepatic TEQ levels, suggesting TEQ-dependent hepatic sequestration. (c) 2005 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.envpol.2005.07.020

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

To establish a monitoring system for gene expression profiles related to chemical contamination in wild common cormorants (Phalacrocorax carbo), the present study constructed an oligo array designed from expressed sequence tag (EST) sequences of the cormorant liver, where 1061 unique oligonucleotides were spotted. Common cormorants were collected from Lake Biwa, Japan in May 2001 and 2002. With the use of this oligo array, gene expression profiles in the liver of individual specimens were evaluated. To determine the expression patterns of genes altered by environmental contaminants, relationships between concentrations of persistent organochlorines including polychlorinated dibenzo-p-dioxins, furans, polychlorinated biphenyls, 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane and its metabolites (DOTS), hexachlorocyclohexane isomers (HCHs), chlordane compounds (CHLs), butyltins, and bisphenol A (BPA) and expression levels of each gene in the cormorant liver were examined using stepwise multiple regression analysis. The reliability of data obtained by the oligo array was further confirmed by quantifying the expression levels of certain genes using real-time RTPCR. The 2,3,7,8-tetrachlorodibenzo-p-dioxin toxic equivalent (TEQ) level was positively correlated with both cytochrome P4501A4 and 1A5 gene expression. In addition, the mRNA level of an antioxidant enzyme, Cu/Zn superoxide dismutase, was negatively correlated with hepatic total TEQ. Other antioxidant enzymes, glutathione peroxidase 3 and glutathione S-transferase class mu, were negatively correlated with HCHs and BPA levels, respectively. The mRNA expression level of a nonenzymatic antioxidant, haptoglobin, was negatively but not significantly correlated with CHLs. These results led to a hypothesis that wild cormorant population may suffer from oxidative stress due to chemically induced formation of reactive oxygen species and subsequent reduction of antioxidant resistance. Thus, the cormorant oligo array may be a useful monitoring tool to identify specific gene expression profiles altered by various environmental contaminants. Although further research is required to clarify a definitive cause-and-effect relationship, the current study provides valuable information on contaminant-responsive genes to predict potential effects on wildlife in a real environment.

DOI： 10.1021/es051386m

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ROYAL SOC CHEMISTRY  

Arsenic concentrations in hair and urine, and urinary levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage, were examined for inhabitants of the Mekong Basin in Kratie Province, Cambodia. Also, the arsenic levels of tube-well water were determined. Total arsenic concentrations in tube-well water ranged from < I to 886 mu g L-1, and 44.8% of these exceeded the WHO drinking water guideline of 10 mu g L-1. Elevated levels of arsenic were observed in the human hair and urine, and also a significant positive correlation was observed between the concentrations in hair and urine. These results suggest that the inhabitants are chronically exposed to arsenic through drinking the tube-well water. Levels of urinary 8-OHdG were higher for the subjects with higher arsenic levels in hair and urine, suggesting that induction of oxidative DNA damage was caused by chronic exposure to arsenic in tube-well water for the inhabitants in Kratie Province. To our knowledge, this is the first report on the oxidative DNA damage caused by chronic exposure to arsenic in groundwater for the inhabitants in Cambodia.

DOI： 10.1039/b513652k

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCI LTD  

Concentrations of As and other trace elements and their association were examined in groundwater (n=25) and human hair (n=59) collected at Gia Lam District and Thanh Tri District, suburban areas of Hanoi, Vietnam, in September 2001. Concentrations of As in the groundwater ranged from < 0.10 to 330 mu g/l, with about 40% of these exceeding WHO drinking water guideline of 10 mu g/l. Also, 76% and 12% of groundwater samples had higher concentrations of Mn and Ba than WHO drinking water guidelines, respectively. Arsenic concentrations in hair of residents in Gia Lam and Thanh Tri Districts (range 0.088-2.77 mu g/g dry wt.) were lower than those in other As-contaminated areas of the world, but were higher than those of people in noncontaminated areas. Concentrations of As and Mn in hair of some individuals from the Gia Lam and Thanh Tri Districts exceeded the level associated with their toxicity and, therefore, a potential health risk of As and Mn is a concern for the people consuming the contaminated water in this area. Cumulative As exposure was estimated to be lower than the threshold levels at the present, which might explain the absence of manifestations of chronic As poisoning and arsenicosis in the residents of Gia Lam and Thanh Tri Districts. To our knowledge, this study revealed for the first time that the residents are exposed not only to As but also Mn and Ba from groundwater in the Red River Delta, Vietnam. (c) 2005 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.envpol.2005.04.033

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCI LTD  

This study determined concentrations of polychlorinated biphenyls (PCBs) and organochlorine compound (OC) pesticides in the milk samples of women from the general population in four locations of Indonesia. The most prevalent residues of OCs were DDTs, PCBs and hexachlorocyclohexane isomers (HCHs), whereas other OCs such as chlordane compounds (CHLs), tris(4-chlorophenyl)methane and hexachlorobenzene were lower. The levels of OCs varied between locations and individuals, with DDTs higher in suburban and rural areas than urban localities, may be due to the differences in food habits and sources between the individuals and locations. Data from Purwakarta site indicated continuing DDT exposure, which may confirm recent usage of DDT in Indonesia. A positive correlation was observed between concentration of OCs in human milk and age of mothers, primiparas women having higher OCs than multiparas, suggesting these parameters play an important role influencing the OC burdens in lactating women. Some individuals accumulated DDTs and HCHs in breast milk close to or even higher than the TDI (tolerable daily intake) guidelines proposed by Health Canada. (c) 2005 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.envpol.2005.04.028

Web of Science

Scopus

PubMed

researchmap

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：OXFORD UNIV PRESS  

This study presents concentrations of polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), and dioxin-like coplanar PCBs (Co-PCBs) in the liver and breast muscle of jungle crows (JCs; Corvus macrorhynchos) collected from Tokyo, Japan. 2,3,7,8-Tetrachlorodibenzo-p-dioxin toxic equivalents (TEQs) derived by WHO bird-TEF were in the range of 23 to 280 pg/g (lipid) in the liver, which are lower or comparable to the lowest-observed-effect-level of CYP induction in chicken, and 5.6-78 pg/g (lipid) in the pectoral muscle. Cytochrome P450 (CYP) 1A-, 2B-, 2C-, and 3A-like proteins were detected using anti-rat CYP polyclonal antibodies in hepatic microsomal fractions. Significant (p < 0.05) positive correlations between hepatic TEQs and CYP1A or CYP3A-like protein expression levels were noticed, implying induction of these CYP isozymes by TEQs. On the other hand, there was no significant positive correlation between muscle TEQ and any one of analyzed CYP isozyme expression levels. CYP1A- and CYP3A-like protein expression levels represented better correlations with pentoxy- and benzyloxyresorufin-O-dealkylase activities rather than methoxy- and ethoxyresorufin-O-dealkylase activities, indicating unique catalytic functions of these CYPs in JCs. Furthermore, we succeeded in isolating CYP1A5 cDNA from the liver of JC, having an open reading frame of 531 amino acid residues with a predicted molecular mass of 60.3 kDa. JC CYP1A5 mRNA expression measured by real-time RT-PCR had a significant positive correlation with hepatic TEQs, suggesting induction of CYP1A5 at the transcriptional level. Ratios of several Co-PCB congeners to CB-169 in the liver of JCs revealed significant negative correlations with CYP1A protein or CYP1A5 mRNA expression levels, implying metabolism of these congeners by the induced CYP1A. The liver/breast muscle concentration (L/M) ratios of PCDDs/DFs and CB-169 increased with an increase in hepatic CYP1A protein or CYP1A5 mRNA expression levels, suggesting congener-specific hepatic sequestrations by the induced CYP1A. The present study provides insights into the propensity of CYP1A induction to the exposure of dioxin-like chemicals, and unique metabolic and sequestration capacities of CYP1A in JC.

DOI： 10.1093/toxsci/kfi326

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

Most toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related planar halogenated aromatic hydrocarbons (PHAHs) are mediated by ligand-activated aryl hydrocarbon receptor (AHR) signaling pathway. To understand the regulation mechanism of AHR and AHR nuclear translocator (ARNT) expression in wild Baikal seal (Pusa sibirica) population contaminated by PHAHs, the present study investigated hepatic mRNA expression levels of AHR and its heterodimer, ARNT genes, in association with biological index (age, gender and body weight), PHAH accumulation and expression levels of cytochrome P450 (CYP) 1A and 1B. While there was no gender difference, the AHR mRNA expression levels were increased with ages (p =0.014) and body weights (p=0.015), indicating that AHR expression might be affected by these biological factors. The AHR mRNA expression levels exhibited significant positive correlations with total TEQs and most of individual congener TEQs derived from polychorinated dibenzo-p-dioxins, dibenzofurans and non-ortho coplanar polychorinated biphenyls (PCBs), indicating the transcriptional up-regulation of AHR expression by these congeners. On the other hand, there was no significant correlation between individual TEQs from mono-ortho coplanar PCBs and AHR expression. These results imply the structure-related transcriptional activity of AHR among PHAHs congeners. AHR mRNA levels showed positive correlations with both CYP1A protein (p=0.039) and CYP1A1 mRNA expression levels (p=0.046). In contrast to AHR expression, neither the total nor individual congener TEQs influenced ARNT at the transcriptional level. ARNT mRNA showed significant negative correlations with CYP1A/1B protein (p = 0.027 and p = 0.006) and CYP1A1 mRNA expression levels (p = 0.039), implying the existence of different transcriptional regulation between AHR and ARNT genes and negative regulation by CYP1A/1B-mediated signaling pathways. The present findings may render significant insight on the basic mechanisms underlying regulation of AHR and ARNT expressions associated with biological factors and PHAH exposure in wild mammalian populations. (C) 2005 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.cca.2005.07.007

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

To assess the significance of waste dumping sites as a source of chemical contamination to ecosystems, we analyzed the residue levels of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), polychlorinated biphenyls (PCBs), and other organochlorines in the breast muscle of crows from a dumping site in the south of Chennai city, South India. Crows from the dumping site contained significantly higher total TEGs (60 +/- 27 pg/g lipid wt) than those from the reference sites (26 +/- 18 pg/g lipid wt). Especially, certain dioxin-like coplanar PCB congeners (Co-PCBs), such as CB-77 and CB-105, whose source iscommercial PCBs,were significantly higher in crows from the dumping site than those from the reference sites. Profiles of PCDDs/DFs and Co-PCBs in crows from the dumping site were similar to those of soil at the same site, which was confirmed by principal component analysis. Furthermore, significant positive correlations were obtained between the congener-specific bioconcentration factors (BCFs) of PCDDs/DFs estimated from concentrations in crows and soil from the dumping site and the theoretical BCFs calculated from water-particle and lipid-water partitioning coefficients. On the other hand, the estimated BCFs had significant negative correlations with the molecular weight of PCDDs/DFs, indicating that molecular size limits their bioaccumulation. These results suggest that dioxin-like congeners in the soil of the dumping site were transferred directly to the crows through the ingestion of on-site garbage contaminated with soil, ratherthan through trophic transfer in the ecosystem. The present study provides insight into the ecological impacts of dumping sites.

DOI： 10.1021/es050057r

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

The aryl hydrocarbon receptor (AHR) mediates the toxic effects of planar halogenated aromatic hydrocarbons (PHAHs). Bony fishes exposed to PHAHs exhibit a wide range of developmental defects. However, functional roles of fish AHR are not yet fully understood, compared with those of mammalian AHRs. To investigate the potential sensitivity to PHAHs toxic effects, an AHR cDNA was initially cloned and sequenced from red seabream (Pagrus major), an important fishery resource in Japan. The present study succeeded in identifying two highly divergent red seabream AHR cDNA clones, which shared only 32% identity in full-length amino acid sequence. The phylogenetic analysis revealed that one belonged to AHR1 clade (rsAHR1) and another to AHR2 clade (rsAHR2). The rsAHR1 encoded a 846-residue protein with a predicted molecular mass of 93.2 kDa, and 990 amino acids and 108.9 kDa encoded rsAHR2. In the N-terminal half, both rsAHR genes included bHLH and PAS domains, which participate in ligand binding, AHR/ARNT dimerization and DNA binding. The C-terminal half, which is responsible for transactivation, was poorly conserved between rsAHRs. Quantitative analyses of both rsAHRs mRNAs revealed that their tissue expression profiles were isoform-specific; rsAHR1 mRNA expressed primarily in brain, heart, ovary and spleen, while rsAHR2 mRNA was observed in all tissues examined, indicating distinct roles of each rsAHR. Furthermore, there appeared to be species-differences in the tissue expression profiles of AHR isoforms between red seabream and other fish. These results suggest that there are isoform- and species-specific functions in piscine AHRs. (c) 2005 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.cca.2005.06.003

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

The present study examines the effects of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and coplanar polychlorinated biphenyls (Co-PCBs) on hepatic cytochromes P450 (CYP) in the wild population of common cormorants from Lake Biwa, Japan, and discusses functional roles of CYP1A in terms of correlation analysis between tissue concentrations of individual congeners and expression levels of CYP1A. Levels of alkoxyresorufin (methoxy-, ethoxy-, pentoxy-, and benzyloxyresorufin) O-dealkylase activities and a protein cross-reacted with anti-rat CYP1A1 polyclonal antibodies showed significant positive correlations with total 2,3,7,8-tetra chlorodibenzo-p-dioxin toxic equivalents (TEQs) or TEQs for most individual congeners in the liver of cormorants, suggesting induction of CYP1A-like protein by these chemicals. In contrast, TEQs for lower chlorinated congeners, 2,3,7,8-T4CDF and PCB77, showed relatively low correlations with the expression level of CYP1A-like protein. Concentrations of 2,3,7,8-T4CDF and PCB77 normalized to a relatively recalcitrant congener, PCB169, were negatively correlated with the CYP1A-like protein level. These results indicate preferential metabolism of those congeners by CYP1A-like protein that was induced by TEQs. Concentration ratios of liver to pectoral muscle for certain congeners significantly increased with an elevation of the CYP1A-like protein level. Comparing the results in the present study with those of previous studies using rodents treated with certain dioxin-like congeners, these congeners in the liver may be sequestered by CYP1A. Levels of cross-reactive proteins with anti-rat CYP2B1, CYP2C6, and CYP3A2 polyclonal antibodies correlated with neither TEQs nor liver/muscle concentration ratios of congeners. We conclude that the potential for CYP1A induction, and metabolism and sequestration of dioxin-like compounds by CYP1A, may be a critical factor for assessing the ecological risk in wild avian species.

DOI： 10.1021/es048771g

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

Wild jungle crows (Corvus macrorhynchos) captured from three different areas of Tokyo were examined to evaluate environmental contamination of dioxins. In addition to the pathologic examination of their whole body, accumulation of dioxins, mRNA expression of the aryl hydrocarbon receptor (AhR), and pentoxyresorufin-O-depenthylase (PROD) activity in the liver were determined. Marked histopathologic changes were observed in the thyroid glands, especially in the crows from the urban downtown area. Levels of dioxins and their toxic equivalents (TEQs) and AhR mRNA expression in the livers of the crows from the urban area were higher than those from the suburban area. There was a high correlation between the levels of TEQs and PROD activity. The results of the present study demonstrated that jungle crows possess AhR-mediated toxicologic pathways similar to those of mammals and suggest the possibility that the thyroidal changes observed in the adult crows from the urban areas are one of the toxic manifestations resulting from exposure to dioxins and other environmental chemicals.

DOI： 10.1007/s00244-004-0101-5

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCI LTD  

Mercury (Hg) concentrations in human hair and fish samples from Phnom Penh, Kien Svay, Tomnup Rolork and Batrong, Cambodia, collected in November 1999 and December 2000 were determined to understand the status of contamination, and age-and sex-dependent accumulation in humans and to assess the intake of mercury via fish consumption. Mercury concentrations in human hair ranged from 0.54 to 190 mug/g dry wt. About 3% of the samples contained Hg levels exceeding the no observed adverse effects level (NOAEL) of WHO (50 mug/g) and the levels in some hair samples of women also exceeded the NOAEL (10 mug/g) associated with fetus neurotoxicity. A weak but significant positive correlation was observed between age and Hg levels in hair of residents. Mercury concentrations in muscle of marine and freshwater fish from Cambodia ranged from <0.01 to 0.96 mug/g wet wt. Mercury intake rates were estimated on the basis of the Hg content in fish and daily fish consumption. Three samples of marine fish including sharp-tooth snapper and obtuse barracuda, and one sample of sharp-tooth snapper exceeded the guidelines by US EPA and by Joint FAO/WHO Expert Committee on Food Additives (JECFA), respectively, which indicates that some fish specimens examined (9% and 3% for US EPA and JECFA guidelines, respectively) were hazardous for consumption at the ingestion rate of Cambodian people (32.6 g/day). It is suggested that fish is probably the main source of Hg for Cambodian people. However, extremely high Hg concentrations were observed in some individuals and could not be explained by Hg intake from fish consumption, indicating some other contamination sources of Hg in Cambodia. (C) 2004 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.envpol.2004.07.015

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

DOI： 10.1016/j.marpolbul.2004.11.041

Web of Science

Scopus

PubMed

researchmap

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

This study presents full-length cDNA sequences of CYP1A1 and 1A2, in common minke whale (Balaenoptera acutorostrata) from the North Pacific. Both CYP1A1 and CYP1A2 cDNAs had an open reading frame of 516 amino acid residues, and predicted molecular masses were 58.3 kDa and 58.1 kDa, respectively. The deduced full-length amino acid sequence of CYP1A1 revealed higher identities with those of sheep (86%) and pig (87%), and that of CYP1A2 was most closely related to human (82%) and monkey CYP1A2 (82%) among species from which CYP1A2 has been isolated so far. Differences in certain conserved and functional amino acid residues of CYP1A1 and 1A2 between common minke whale and other mammalian species indicate the possibility of their specific metabolic function. Concentrations of organochlorine compounds (OCs) including PCBs and DDTs analyzed in common minke whale liver showed no significant correlation with hepatic mRNA expression levels of CYP1A1 and CYP1A2, indicating no induction of these enzymes by such OCs. (c) 2005 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.marpolbul.2005.07.012

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

Concentrations of trace elements (V, Cr, Mn, Co, Cu, Zn, Ga, Se, Rb, Sr, Mo, Ag, Cd, Sn, Sb, Cs, Ba, Hg, Tl, Pb and Bi) were determined in muscle and liver of 12 species of marine fish collected from coastal areas in Malaysia. Levels of V, Cr, Mn, Co, Cu, Zn, Ga, Sr, Mo, Ag, Cd, Sri, Ba and Pb in liver were higher than those in muscle, whereas Rb and Cs concentrations showed the opposite trend. Positive correlations between concentrations in liver and muscle were observed for all the trace elements except Cu and Sn. Copper, Zn, Se, Ag, Cd, Cs and Hg concentrations in bigeye scads from the east coast of the Peninsular Malaysia were higher than those from the west, whereas V showed the opposite trend. The high concentration of V in the west coast might indicate oil contamination in the Strait of Malacca. To evaluate the health risk to Malaysian population through consumption of fish, intake rates of trace elements were estimated on the basis of the concentrations of trace elements in muscle of fish and daily fish consumption. Some specimens of the marine fish had Hg levels higher than the guideline value by US Environmental Protection Agency (EPA), indicating that consumption of these fish at the present rate may be hazardous to Malaysian people. To our knowledge, this is the first study on multielemental accumulation in marine fish from the Malaysian coast. (c) 2005 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.marpolbul.2005.06.007

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

In this study, concentrations of dioxins and related compounds (DRCs)-such as polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, and coplanar polychlorinated biphenyls-were found in human breast milk from women living near dumping sites of municipal waste and reference sites in India, Cambodia, Vietnam, and the Philippines during 1999 to 2000. DRCs were detected in all human breast milk samples analyzed, demonstrating that residents in these Asian developing countries have been exposed to these contaminants. In India, the concentrations of DRCs in human breast milk from women living near the investigated dumping site were notably higher than those from women living near reference sites and from women in other Asian developing countries. Toxic equivalent quantity (TEQ) levels of DRCs were comparable with or higher than those reported in the general populations of developed countries since 1990. In contrast, levels of these contaminants in human breast milk in women from Cambodia and Vietnam were not significantly different between milk from women living near the dumping and reference sites. These results indicate that significant pollution sources for DRCs are present in Indian dumping sites and that residents there have been exposed to relatively higher levels of these contaminants. TEQ levels in human breast milk from the dumping site in India tended to decrease with an increase in the number of previous deliveries by mothers, whereas no significant relationship was observed in Cambodia, Vietnam, or the Philippines. This suggests that mothers who have been exposed to relatively high levels of DRCs transfer greater amounts of these contaminants to the first infant than later ones through breast-feeding, which in turn implies that the first children of these mothers might be at higher risk from DRCs. When the residue levels of DRCs in bovine milk collected from the Indian dumping site and reference sites were examined, TEQ levels in bovine milk from the dumping suggests that bovine milk is a potential source of DRCs for residents living near the dumping site in India. To our knowledge, this is the first comprehensive study on exposure to DRCs of residents living in proximity to open dumping sites of municipal waste in Asian developing countries.

DOI： 10.1007/s00244-004-3172-4

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCI LTD  

The contaminant-induced cytochrome P450 (CYP) members in minke whale (Balaenoptera acutorostrata) can be potential biomarkers of the contaminant exposure and toxic effects. In this study, we constructed a cDNA library from the liver of minke whale from the North Pacific, and further screened a total of 6930 clones randomly selected in the library for the isolation of cDNA clones encoding novel members of CYP superfamily. The screening revealed the isolation of six novel CYP cDNA clones that are classified into CYP1A, CYP2C, CYP2E, CYP3A, CYP4, and CYP4A subfamilies. The BLAST homology search using the partial cDNA fragments of four CYP subfamilies (CYP1A, CYP2C, CYP2E and CYP4A) demonstrated that the minke whale CYPs were most closely related to pig CYPs (81-91%). Identification of multiple CYP genes in marine mammal species such as minke whale will provide new insights into the metabolic or toxicological functions of individual CYP members. (C) 2004 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.marenvres.2004.03.035

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCI LTD  

Concentration of butyltin compounds (BTs), including tributyltin (TBT), dibutyltin (DBT) and monobutyltin (MBT) and total tin (SigmaSn) were determined in green mussel (Perna viridis), 10 species Of Muscle fish and sediment from coastal waters of Malaysia. BTs were detected in all these samples ranging from 3.6 to 900 ng/g wet wt., 3.6 to 210 ng/g wet wt., and 18 to 1400 ng/g dry wt. for mussels, fish and sediments, respectively. The concentrations of BTs in several locations of this study were comparable with the reported values from some developed countries and highest among Asian developing nations. Considerable concentration of BTs in several locations might have ecotoxicological consequences and may cause concern to human health. The parent compound TBT was found to be highest than those of its degradation compounds, DBT and MBT, suggesting recent input of TBT to the Malaysian marine environment. Significant positive correlation (Spearman rank correlation: r(2) = 0.82, P < 0.0001) was found between BTs and SigmaSn, implying considerable anthropogenic input of butyltin compounds to total tin contamination levels. Enormous boating activities may be a major source of BTs in this country, although aquaculture activities may not be ignored. (C) 2004 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.envpol.2004.01.002

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCI LTD  

The toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and its related planar halogenated aromatic hydrocarbons (PHAHs) are mediated by the aryl hydrocarbon receptor (AHR). To investigate the potential sensitivity to PHAHs and the evolutional diversity of AHR in aquatic birds, AHR cDNAs were initially cloned and sequenced from the livers of a black-footed albatross (Diomedea nigripes) and a common cormorant (Phalacrocorax carho). In this study, we report the identification of two distinct AHR paralog genes in these species. The two full-length AHR cDNAs from albatross were highly divergent (33% overall amino acid identity, and 60% identity in the N-terminal half). Phylogenetic analysis showed that one of them belongs to the AHR1 clade and the other one to the AHR2 clade, which has been identified only from fishes, but not yet from mammals and birds. Albatross AHR1 encoded a 861-residue protein with a predicted molecular mass of 96.7 kDa, and in the case of albatross AHR2, 925 amino acids and 100.7 kDa. From cormorant liver, the full-length AHR1 cDNA and the partial AHR2 cDNA were cloned. This result strongly suggests that bird species also possess two distinct AHR genes (AHR1 and AHR2). To our knowledge, this is the first report on the presence of an AHR2-like isoform in bird species as well as in fish. (C) 2004 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.marenvres.2004.03.004

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCI LTD  

Constitutive androstane receptor (CAR) plays a key role in the transcriptional regulation of CYP2B, 2C and 3A genes in response to phenobarbital, ortho-chlorine substituted polychlorinated biphenyls (PCBs) and sex steroids in rodents and human. However, studies addressing CAR are limited to certain laboratory animals and cell lines, and there is little information on the presence of CAR and its physiological and contaminant-related functions in wildlife. While aquatic mammals including seal species are at the top of food chain and highly contaminated by xenochemicals such as PCBs, induction of CYP2/3 subfamilies by such chemical exposure and their regulatory mechanisms have not yet been established in these animals. To investigate mechanisms of CAR-CYP's signaling pathways in aquatic mammals, we initially attempted to isolate CAR cDNA in the liver of northern fur seals (Callorhinus ursinus) from off-Sanriku, Japan. The full-length CAR cDNA had an open reading frame of 1047 bp that encodes a protein containing 348 amino acids. Comparison of the amino acid sequence of CAR from the fur seal with those from other mammalian species showed high identities with CARs from human (83%), monkey (82%), rat (73%) and mouse (73%), revealing a conservation of CAR among the mammalian species. Phylogenetic analysis demonstrated that the fur seal CAR was classified into CAR clade and not into PXR/BXR or VDR clade, suggesting the CARs would be conserved among, divergent mammals including aquatic species. With our concomitant paper, where CAR cDNA isolation from the liver of Baikal seal is reported (Iwata et al., in preparation), to our knowledge, this is the first study on the identification of CAR cDNA from wildlife species. (C) 2004 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.marenvres.2004.03.003

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

Concentrations of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and coplanar polychlorinated biphenyls (Co-PCBs) were determined in the liver and pectoral muscle of common cormorants (Phalacrocorax carbo) collected from Lake Biwa, Japan. To clarify the toxicokinetic behaviors and potential toxicities of these chemicals, the present study addresses life-stage- and tissue-specific accumulation of the congeners. Total 2,3,7,8-tetrachlorodibenzo-p-dioxin toxic equivalents (TEQs) were in the range of 360 to 50 000 pg/g lipid weight in the liver and 310 to 12 000 pg/g lipid weight in the pectoral muscle. Among congeners, for which toxic equivalency factors were assigned, PCB126, 2,3,4,7,8-P5CDF, and 1,2,33,8-P5CDD made a greater contribution to total TEQs in the liver. Hepatic concentrations of T-4- to H6CON, P-5- and H(6)CDFs, and Co-PCBs (except PCB77) significantly increased with growth of cormorants, leading to life-stage-related compositional changes. The concentration ratios of liver to pectoral muscle revealed preferential accumulation of higher chlorinated congeners in hepatic tissue. For most congeners, concentration ratios significantly increased with an increase in hepatic total TEQs, suggesting their con centration-dependent hepatic sequestration. These results imply the presence of hepatic binding protein(s) such as cytochrome P450, inducible by these chemicals, which may function as a binding species different from aryl hydrocarbon receptor. On the basis of these results, we conclude that the toxicokinetic behavior of each congener is life-stage-, tissue-, and concentration-dependent. TEN in wildlife populations exposed to multiple congeners with varying concentrations should be used with caution for risk assessment, even within a species.

DOI： 10.1021/es0494858

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

To assess the toxicokinetic behavior and potential toxicity of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and coplanar polychlorinated biphenyls (PCBs) in Baikal seals, congener-specific levels and tissue distribution were evaluated in the liver and blubber, and the effects of biological factors including sex and growth were assessed. Total 2,3,7,8-TCDD toxic equivalents (TEQs) were in the range of 210-920 pgTEQ/g fat wt (180-800 pgTEQ/g wet wt) in the blubber and 2907800 pgTEQ/g fat wt (10-570 pgTEQ/wet wt) in the liver. Non-ortho coplanar PCB126 was the most TEQ-contributed congener accounting for 37-59% of the total THIS in the liver. From the unique congener profiles, weak metabolic properties of Baikal seals for 2,3,7,8-TCDF and 1,2,3,7,8-P-5-CDF are suggested. Concentrations of most congeners linearly increased with age in male seals, whereas in adult females the levels revealed an age-related decline. The increasing and declining rates were congener-specific. Maternal transfer rates of 5 representative congeners from adult female to pup through lactation, which was estimated from male-female differences in the body burden, was 1.1 ngTEQ/kg/day for the first pup and decreased with every lactational epoch. The liver-blubber distribution of 1,2,3,4,7,8-H6CDD, 1,2,3,6,7,8-H6CDD, PCB81, PCB126, and PCB169 was dependent on the hepatic total TEQ, indicating hepatic sequestration by induced cytochrome P450 (CYP). These results indicate that congener profile in Baikal seals is governed by complex factors including sex, tissue concentration, binding to CYP, and rates of absorption and meta bolism/excretion.

DOI： 10.1021/es035461

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCI LTD  

Despite the ban on persistent organochlorines (OCs) in most of the developed nations, their usage continued until recently in many Asian developing countries including Vietnam, for agricultural purposes and vector-borne disease eradication programs. In this study. we collected human breast milk samples from the two big cities in Vietnam: Hanoi (n = 42) and Hochiminh (n = 44) and determined the concentrations of persistent OCs such as PCBs, DDT and its metabolites (DDTs), hexachlorocyclohexanes (HCHs), hexachlorobenzene (HCB). chlordane compounds (CHLs) and tris-4-chlorophenyl-methane (TCPMe). The contamination pattern of OCs was in the order of DDTs > PCBs > HCHs > CHLsapproximate toHCBapproximate toTCPMe. Compilation of available data indicated that DDT residue levels in human breast milk from Vietnam were among the highest values reported for Asian developing countries as well as developed nations. This result suggests recent usage of DDTs in both north and south Vietnam. Interestingly, in both cities, the p,p'-DDT portion was higher in multiparas than those in primiparas. Considering the fact that the interval between the first and the second child of a mother in Vietnam is usually short, this result probably indicates continuous intake of DDTs in the population. Analysis of infant exposure to DDTs via breast milk suggested that the daily intake rates for number of individuals are close to or above the threshold for adverse effects which may raise concern on children health. (C) 2004 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.envpol.2003.11.012

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER-VERLAG  

Wide ranges of organochlorine residues were determined in the blubber of franciscana (Pontoporia blainvillei), estuarine dolphin (Sotalia guianensis), Atlantic spotted dolphin (Stenella frontalis), and long-beaked common dolphin (Delphinus capensis) incidentally caught along Brazilian coastal waters. Concentrations of DDTs and PCBs were the highest, followed by CHLs, TCPMOH, dieldrin, TCPMe, heptachlor epoxide, HCB, and HCHs. Unexpectedly, significant pollution of PCBs, DDTs, TCPMe, and TCPMOH were observed in cetaceans from Brazil, implying the occurrence of local sources in the Southern Hemisphere comparable to those in the Northern Hemisphere, probably by high industrialization in Brazil. On the other hand, CHLs, HCB, HCHs, heptachlor epoxide, and dieldrin residue levels in Brazilian dolphins were much lower than those in other species from the Northern Hemisphere. Significant correlations of TCPMe and TCPMOH were found along with PCBs and DDTs, indicating the highly bioaccumulative nature of all these compounds and/or possible similar pollution sources.

DOI： 10.1007/s00244-003-2239-y

Web of Science

Scopus

PubMed

researchmap

researchmap

researchmap

Language：English  

DOI： 10.11299/brte.15.339

CiNii Books

researchmap

Other Link： http://search.jamas.or.jp/link/ui/2006162573

Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

DOI： 10.1016/S0025-326X(03)00189-9

Web of Science

Scopus

PubMed

researchmap

DOI： 10.11403/jset.6.1

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCI LTD  

Species differences in sensitivity to related planar halogenated aromatic hydrocarbons (PHAH) add significant uncertainty in assessing the ecological risk to aquatic mammals. To investigate mechanisms of PHAH sensitivity in aquatic mammals, we cloned and sequenced the cDNA of Baikal seal aryl hydrocarbon receptor (AHR), an intracellular protein that initiates PHAH-mediated effects. The Baikal seal AHR cDNA has an open reading frame of 843 amino acid residues with a predicted molecular mass of 94.6 kDa. Comparison of AHR amino acid sequences indicated a high degree of sequence conservation (98%) between Baikal and harbor seals. The high conservation of AHRs between Baikal and harbor seals indicates that these seals express AHR proteins closely related structurally. In our previous report (Kim & Hahn, 2002), the dioxin-binding affinity of the harbor seal AHR was at least as high as that of the AHR from a dioxin-sensitive strain of mice, suggesting that this seal species may be sensitive to PHAH effects. This implies that Baikal seal may also be sensitive to dioxin effects. (C) 2002 Elsevier Science Ltd. All rights reserved.

DOI： 10.1016/S0141-1136(02)00180-0

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY  

Polychlorinated biphenyls (PCBs), including coplanar congeners, hexachlorocyclohexane isomers, chlordane-related compounds, and hexachlorobenzene, were found in the breast muscle of Steller's sea eagles (SSE) and white-tailed sea eagles (WSE) threatened species, collected in Hokkaido, Japan, during the two years from 1998 to 1999. Both PCBs and DDTs were the most notable compounds, with concentrations one to two orders of magnitude higher than the other compounds, that is, from 120 to 39,000 and from 68 to 15,000 ng/g wet weight, respectively. Non-ortho (International Union of Pure and Applied Chemistry [IUPAC] 77, 126, and 169) and mono-ortho (IUPAC 105, 118, and 156)-substituted coplanar PCB congeners amounted to 9.2 to 740 pg/g of 2,3,7,8-tetrachlorodibenzo-p-dioxin toxic equivalents derived from the World Health Organization, Paris, France (WHO), toxic equivalent factors. The atmospheric PCBs and DDTs in eastern Siberian cities, such as Khabarovsk and Magadan, have been reported to be much higher than Hokkaido and the North Pacific. Thus, we speculated that the eagles might have been contaminated in these areas, where they spend most of the year except winter, which they spend in eastern Siberia. Adult eagles accumulated more PCBs and DDTs than younger ones. The patterns of PCB congeners were also found to change, depending on the age of the eagle examined; adult eagles showed relatively higher proportions of highly chlorinated PCBs than juvenile eagles did. This difference would be related to the efficiency of the excretion and the metabolism of each PCB congener in the eagles.

DOI： 10.1002/etc.5620210422

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY  

From 16 largha seats (Phoca largha) and 15 ribbon seals (Phoca fasciata) in the coastal waters of Hokkaido, Japan, blubber chlorinated hydrocarbon (CHC) levels and hepatic cytochrome P450 (CYP) catalytic activities and their immunochemically detected protein content levels were measured. Concentrations of DDTs (2,2-bis(4-chlorophenyl)-1,1-dichloroethylene,p,p'-DDE; 2,2-bis(4-chlorophenyl)-1,1-dichloroethane,p,p'-DDD; dichlorodiphenyltrichloroethane, p,p'-DDT), polychlorinated biphenyl congeners (PCBs), and chlordane compounds (oxychlordane, chlordanes, and nonachlors) in both species were in the range of 290 to 5,300, 420 to 4,000, and 130 to 1,500 ng/g lipid weight, respectively. Aryl hydrocarbon receptor (AhR) agonists, non-ortho (IUPAC 77 and 126) and mono-ortho (IUPAC 105, 118, and 156) coplanar PCB congeners, were also detected, and the 2,3,7,8-tetrachlordibenzo-p-dioxin (TCDD) toxic equivalents (TEQs) were 4.9 to 120 pg TEQ/g lipid weight. Cross-reactive proteins with polyclonal antibodies against rat CYP1A1 and CYP3A2 were notably detected in seal liver microsomes. Interestingly, a polyclonal antibody against rat CYP2B1 recognized proteins only at trace levels. In largha seals, both levels of alkoxyresorufin- (methoxy-, ethoxy-, pentoxy-, and benzyloxyresorufin) O-dealkylase (AROD) activities and proteins detected by polyclonal antibodies against rat CYP1A1 were significantly correlated with the concentrations of individual coplanar PCB congeners, total TEQs, and total PCBs. Threshold concentrations for TEQs in blubber of the largha seal to induce hepatic CYP1A protein and EROD activity were estimated to be 8.5 and 19 pg TEQ/g fat weight, respectively. In ribbon seals, similar correlations were not detected, although the TEQ levels were not significantly lower than those in largha seals. These results suggest that AROD activity and CYP1A1 protein in the liver of the largha seal could be a biomarker for the exposure to AhR agonists such as coplanar PCB congeners. This study also indicates differences in AhR-mediated responses to the CHC exposures between largha and ribbon seals.

DOI： 10.1002/etc.5620210416

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

The mammalian constitutively active receptor (CAR) is a novel ligand-activated transcription factor that participates in controlling the expression of cytochrome P450 2B (CYP2B) genes in response to pharmaceutical agents (phenobarbital) and halogenated aromatic hydrocarbons (ortho-substituted PCBs). The occurrence and physiological function of this protein are as yet unknown in marine animals, where there has been a paradoxical lack of induction by PB-type chemicals. One approach to understanding CAR function is to study the evolutionary history of processes such as CAR-CYP2B coupling. In this study, CAR function was evaluated in a representative teleost fish (scup, Stenotomus chrysops). Treatment of scup with 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP), which is one of the most potent CYP2B inducers in mouse, caused no increase in hepatic alkoxyresorufin O-dealkylase activity nor in immunodetectable CYP2B-like protein levels. Western blot analyses of scup livers using anti-human CAR antisera revealed the occurrence of a putative CAR homologue in nuclear and cytoplasmic fractions, but no nuclear accumulation of CAR following TCPOBOP treatment, which is a first step regulating the transcriptional activation of CYP2B genes in mouse. Immunohistochemical study also showed no translocation of CAR into nucleus in the hepatocytes of TCPOBOP-treated scup. These results suggest that there may be species-specific differences in CAR activation or CAR-CYP2B coupling signaling transduction in fish from those in mouse. © 2002 Elsevier Science Inc. All rights reserved.

DOI： 10.1016/S1532-0456(02)00038-8

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

Organochlorine (OCs) and butyltin (BTs) residues were determined in deep-sea organisms collected from the western North Pacific, off-Tolioku, Japan. Among OCs, concentrations of polychlorinated biphenyls (PCBs') and DDTs (DDTs and its metabolites) were the highest in deep-sea organisms (maximum concentrations of 6700 and 13,000 ng/g lipid wt, respectively). Chlordane compounds (CHLs) were the next most abundant OCs. and hexachlorocyclohexanes (HCHs) and hexachlorobenzene (HCB) were the lowest. BTs were also detected at maximum concentrations of 570 ng/g wet wt. Concentrations of PCBs, CHLs and BTs in deep-sea organisms collected front the western North Pacific, off-Tohoku, were generally lower than those in deep-sea and shallow water organisms from Japanese coastal waters. On the other hand, considerable variations in the concentrations of OCs were found among deep-sea organisms analyzed. Several carnivorous fishes such as snubnosed eel. lanternshark and grenadiers accumulated some OCs such as PCBs, DDTs and CHLs at high concentrations of up to a few mug/g levels. In addition, the residue pattern of OCs and BTs in fishes showed a specific trend according to the sampling depth; higher concentrations of PCBs, DDTs and CHLs and lower concentrations of HCHs, HCB and BTs were found in fishes collected from greater depth (similar to1000 m) compared to those from shallower waters. This trend is consistent with the results of our earlier study on mesopelagic myctophid fishes. Results of this study suggest vertical transport of hydrophobic OCs such as PCBs, DDTs and CHLs and its accumulation in benthic deep-sea organisms. (C) 2002 Elsevier Science Ltd. All rights reserved.

DOI： 10.1016/S0025-326X(02)00100-5

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

Concentrations of persistent organochlorines (OCs) such as PCBs, DDTs, chlordanes (CHLs), HCHs and HCB were determined in the liver of bluefin tuna (Thunnus thynnus) collected from Japanese coastal waters in order to elucidate accumulation profiles and to evaluate the suitability of this species as a biomonitor for pollution in the open sea ecosystem. Concentrations of PCBs, DDTs and CHLs in bluefin tuna increased significantly with body length (30-190 cm). HCHs and HCB residues were comparable among all the sampling regions, and the levels of these chemicals did not show correlation with body length. These results suggest significance of dietary uptake of PCBs, DDTs and CHLs compared to the intake via the gill. On the other hand, equilibrium partitioning with ambient water is a major determinant of the levels of HCHs and HCB in tuna. Body-Length Normalized Values (BLNV) of PCBs, DDTs and CHLs concentrations in bluefin tuna were calculated using the linear regression equation obtained from the plot of concentrations and body length. BLNV of these chemicals on a lipid wt basis, which was adjusted for 100 cm body length, were indicative of the present state water pollution by PCBs, DDTs and CHLs. These results suggest that bluefin tuna is a suitable bioindicator for monitoring OCs contamination in the open sea ecosystem. (C) 2002 Elsevier Science Ltd. All rights reserved.

DOI： 10.1016/S0025-326X(02)00109-1

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

Naturally occurring neurotoxins, 6,7-dihydroxy-1,2,3,3-tetrahydroisoquinolines (DHTIQs), thought to be the causative agents of Parkinsonism. DHTIQs including norsalsolinol have been found in the mammalian central nervous system. Norsalsolinol can be formed by a non-enzymatic Pictet-Spengler condensation reaction between dopamine and formaldehyde, and has been detected in the urine of Parkinsonian patients. However, the effects of DHTIQs on the secretion of dopamine, as well as other neurotransmitters, are not well understood. This study investigated the effects of norsalsolinol on dopamine secretion from nerve growth factor-differentiated PC12 cells. Norsalsolinol (1-100 muM) pretreatment suppressed both ATP (100 muM)- and K(+) (50 mM)-induced dopamine secretion from PC12 cells in a concentration-dependent fashion, but did not affect basal dopamine secretion. In beta -escin-permeabilized PC12 cells, norsalsolinol pretreatment suppressed Ca(2+) (pCa = 4-8)-induced dopamine secretion, but did not inhibit the secretagogue-induced change in intracellular Ca(2+) concentration. These results suggest that norsalsolinol causes the inhibition of secretagogue-induced dopamine secretion from PC12 cells without altering intracellular Ca(2+) concentration. Inhibition of dopamine secretion by norsalsolinol may also be involved in postural abnormality in Parkinson's disease. (C) 2001 Elsevier Science Ltd. All rights reserved.

DOI： 10.1016/S0197-0186(00)00121-2

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

Chlorinated hydrocarbon (CHC) levels in the blubber of larga seals (Phoca largha) and ribbon seals (Phoca fasciata) collected from the coastal waters of Hokkaido, Japan, were determined in order to assess the hormonal effects of CHC exposure in free-ranging pinnipeds. Plasma thyroid hormone levels, including total thyroxine (T4), free thyroxine (free T4), total triiodothyronine (T3), and free triiodothyronine (free T3), were also measured. Higher concentrations of polychlorinated biphenyl congeners (PCBs), dichlorodiphenyltrichloroethane and its metabolites, and chlordane compounds were found in the range of 380 to 2,600 ng/g, 350 to 2,600 ng/g, and 120 to 760 ng/g on a wet-weight basis, respectively. Spearman rank correlation analyses showed that in larga seals, plasma total T3 and free T3 levels negatively correlated with levels of all the CHCs analyzed, although there was no such correlation between total or free T4 levels and CHC concentrations. In ribbon seals, total T3 levels significantly decreased with an increase of di-ortho PCB (PCB 170 and 180) residues. These findings indicated that the plasma T3 deficiency could be associated with some CHC exposure in larga and ribbon seals and that the responses of plasma thyroid hormones may be useful biomarkers for CHC exposure in ribbon seals.

DOI： 10.1897/1551-5028(2001)020<1092:NCBPTH>2.0.CO;2

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Chlorinated hydrocarbon (CHC) levels in the blubber of larga seals (Phoca largha) and ribbon seals (Phocafasciata) collected from the coastal waters of Hokkaido, Japan, were determined in order to assess the hormonal effects of CHC exposure in free-ranging pinnipeds. Plasma thyroid hormone levels, including total thyroxine (T4), free thyroxine (free T4), total triiodothyronine (T3), and free triiodothyronine (free T3), were also measured. Higher concentrations of polychlorinated biphenyl congeners (PCBs), dichlorodiphenyltrichloroethane and its metabolites, and chlordane compounds were found in the range of 380 to 2, 600 ng/g, 350 to 2, 600 ng/g, and 120 to 760 ng/g on a wet-weight basis, respectively. Spearman rank correlation analyses showed that in larga seals, plasma total T3 and free T3 levels negatively correlated with levels of all the CHCs analyzed, although there was no such correlation between total or free T4 levels and CHC concentrations. In ribbon seals, total T3 levels significantly decreased with an increase of di-ortho PCB (PCB170.and 180) residues. These findings indicated that the plasma T3 deficiency could be associated with some CHC exposure in larga and ribbon seals and that the responses of plasma thyroid hormones may be useful biomarkers for CHC exposure in ribbon seals.

DOI： 10.1002/etc.5620200521

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

The impact of environmental pollution on selected animals was tested by monitoring the hepatic content of cytochromes P450 and their enzyme activities or by calculating TEQ values from the concentration of pollutants in the body. Fish-eating Stellars Sea Eagles, Haliaeetus pelagicus, found dead in the northern part of Hokkaido island accumulated high levels of PCBs and DDT and metabolites. The TEQ values calculated from the PCB concentration in the eagles were high enough to cause a significant toxic effect in other birds living in the same environment. Some of these birds were also contaminated with high concentrations of lead. Spotted seals, Phoca largha, captured along the coast-line of Hokkaido accumulated PCBs in their fat at about 100 million times the concentrations in the surface sea water. The levels of expressions of hepatic microsomal CYP 1A1 and related enzyme activities in these seals showed good correlation to the levels of PCBs accumulated in the fat. The fresh water crabs, Eriocheir japonicus, were captured from three different rivers with various degrees of pollution. The P450 content and the related enzyme activities showed good correlation to TEQ values obtained from the concentrations of PCBs and PCDDs in the crabs from the rivers. The wild rodents, Clethrionomys rufocanus, were captured from urban, agricultural, and forest areas in Hokkaido. Those from the forest area had the lowest CYP content and related enzyme activities, comparable to those in laboratory-raised animals. Those from the urban areas, presumably contaminated with PAHs from fuel combustion, showed increased CYP 1A1 content and related enzyme activities. Those from the agricultural areas showed increased levels of CYP 1A1, 2B, 2E1. Rats treated with some of the agrochemicals used in the area resulted in a similar pattern of induction. It is concluded that P450 can be a useful biomarker for assessing the environmental impact of chemical pollutants on wild animals.

DOI： 10.1080/135475001452751

Scopus

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ACADEMIC PRESS INC  

Knowledge about the expression sites of cytochrome P450 1A (CYP1A) mRNA is crucial for a better understanding of the physiological function of CYP1A. We investigated the cellular localization of CYP1A mRNA in chemically untreated fish by use of an in situ reverse transcription-polymerase chain reaction (IS RT-PCR technique. The fathead minnow (Pimephales promelas) was formalin-fixed, and paraffin-embedded. Sections (5 mu m) were treated with trypsinogen. Following reverse transcription of CYP1A mRNA, the cDNA was amplified in situ by PCR with specific primers. Detection of the amplicons was accomplished by a second PCR performed with digoxigenin-labeled dUTP. CYP1A mRNA expression was detected in cytoplasm of chondroid cells surrounding hyaline cartilage in gill arches. This result was consistent with that of immunohistochemical analysis with a CYP1A1-specific monoclonal antibody. CYP1A mRNA also was found in stratified squamous epithelium of the pharynx and gill arches, but no staining was detected in those cells by immunohistochemical analysis. The results indicate that IS RT-PCR is an effective/sensitive technique for localizing low level CYP1A expression. In addition, the sites where we identified expression of CYP1A are targets of retinoic acid, sonic hedgehog and Hox genes, suggesting that functional CYP1A in vertebrates could participate in craniofacial skeletal development through involvement in the retinoic acid signaling cascade. (C) 2000 Academic Press.

DOI： 10.1006/bbrc.2000.2543

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Marine mammals, being endangered by the chronic exposure of hydrophobic environmental contaminants as an assorting result of global pollution, are especially focused as indicators for organochlorine pollution. The use of contaminant-induced xenobiotic metabolizers, particularly P450 (CYP) 1A, in marine mammals can be effective as potential biomarkers of the contaminant exposure and/or toxic effects. In this study, we identified the first marine mammalian CYPs. Six novel CYP1A cDNA fragments were cloned from the livers of marine mammal species, minke whale (Balaenoptera acutorostrata), dall's porpoise (Phocoenoides dalli), steller sea lion (Eumetopias jubatus), largha seal (Phoca largha), and ribbon seal (Phoca fasciata) by the method of reverse transcription/polymerase chain reaction (RT/PCR)
two distinct fragments were from steller sea lion and one fragment each was obtained from the other species. Five of the fragments, one from each species, were classified in the subfamily of CYP1A1, and the other fragment cloned from steller sea lion was designated CYP1A2. Degenerate PCR primers were used to amplify the fragments from liver cDNAs. The deduced amino acid sequences of these fragment CYP1As showed identities ranging from 50.0 to 94.3% with other known vertebrate CYPs in the subfamily of CYP1A, including those from fish, chicken, and terrestrial mammals. The isolated fragments were used to construct a molecular phylogeny, along with other vertebrate CYP1A cDNAs cut down in size to the corresponding region of 265 bp in which those newly determined fragments were cloned. This phylogenetic analysis by the maximum parsimony method using the PHYLIP program suggests two distinct evolutional pathways for aquatic mammalian CYP1As, compatible to a conservative taxonomy. Pinniped genes are clustered together with dog gene, forming a carnivore group, and cetaceans form another branch. Identification of CYP1A genes in marine mammals will be an introductory step to provide new insights into the metabolic or toxicological functions of CYP1As in these animals. (C) 2000 Elsevier Science B.V.

DOI： 10.1016/S0166-445X(00)00113-2

Scopus

PubMed

researchmap

Language：Japanese  

DOI： 10.11353/sesj1988.13.51

CiNii Books

researchmap

Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：WILD BIRD SOC JAPAN  

Chronic exposure to man-made chemicals, particularly chlorinated hydrocarbons, in raptors has been associated with reproductive impairment and population declines. In addition, incidents of sub-lethal and lethal lead poisoning in raptors through ingestion of spent gunshot have been reported. However, little information is available on the contaminant levels of Steller&apos;s Sea Eagle (SSE: Haliaeetus pelagicus) and White-tailed Sea Eagle (WSE: H. albicilla) from Hokkaido, Japan. The objective of this study was to determine the levels of toxic contaminants including polychlorinated biphenyls (PCBs), organochlorine pesticides, and lead in sea eagles wintering in Hokkaido, and to evaluate the ecotoxicological risk based on their concentrations. SSEs and WSEs which were found dead or debilitated and subsequently died in Hokkaido from 1986 to 1998 were analysed.
All eagles contained detectable amounts of PCBs, DDTs, hexachlorocyclohexane isomers, chlordane related compounds, and hexachlorobenzene. The highest concentrations of PCBs and DDTs in breast muscles were 18,000 and 17,000 ng/g (wet weight), respectively. Furthermore, non-ortho and mono-ortho substituted coplanar PCB congeners were also detected, leading to 60-540 pg/g of 2,3,7,8-tetrachlorodibenzo-p-dioxin toxic equivalents derived from WHO toxic equivalence factors in the breast muscles. Our previous survey of contaminants in the Far East showed that atmospheric concentrations of PCBs and DDTs in Khabarovsk and Magadan were much higher than those in Hokkaido and North Pacific, suggesting the potential that some east Siberian cities might be a source of contamination found in eagles. Residue levels of PCBs and DDTs in breast muscles of SSEs were comparable to those of raptors collected after the 1980s from North America. Risk assessments based on the residue levels of coplanar PCB congeners and p,p&apos;-DDE detected in these eagles indicated their potential of hepatic cytochrome P450 1A induction and eggshell thinning.
High lead concentrations of over 10,000 ng/g (dry weight) were detected in the livers of some SSEs and WSEs. Three of six dead or moribund SSEs (50%) and three of three WSEs (100%) with livers analyzed for lead died from lead poisoning. Five of the six lead poisoned eagles had lead bullet fragments in their gizzards. The hair of deer was found along with a lead fragment in the intestine of a SSE. In Hokkaido, whole and partial carcasses of deer shot by hunters are left in the field. These are potential sources of lead fragments that are ingested by scavenging raptors during and after the hunting season. Therefore, secondary poisoning by the lead fragment embedded in the tissue of deer is implicated as the main cause of death. Mercury and cadmium concentrations in the tissue of these species were low, implying that the toxicities of these elements were negligible.

Web of Science

researchmap

Language：Japanese   Publisher：社団法人 環境科学会  

Concentrations of V, Cr, Mn, Co, Cu, Zn, Se, Rb, Sr, Mo, Ag, Cd, Sb, Cs, Ba, Hg, T1 and Pb were determined in the livers, kidneys and muscles of Steller&#039;s sea eagle (Haliaeetus pelagicus) and white-tailed sea eagle (H. albicilla) from Hokkaido and golden eagle (Aquila chrysaetos) from Iwate. In general, V, Ag, Cs and Rb concentrations in the liver of raptors were found to be higher than those in other birds reported. Hg and Cd concentrations in the liver of all the raptors were low, but high Pb concentratios were detected in some raptors which remained the lead bullet in the gizzard. A significant positive correlation between Pb and Sb concentrations was observed in the liver of these raptors, indicating that Sb is a useful marker element to evaluate whether lead has been derived from bullet.

DOI： 10.11353/sesj1988.13.51

researchmap

The composition and loads of organochlorine pesticides (DDTs, HCBs, HCHs, CHLs) and polychlorinated biphenyls (PCBs) transported with the Vistula River waters to the Gulf of Gdansk in 1991-1992 has been determined. The method of organochlorine compounds measurement was capillary gas chromatography with ECD after adsorption of the analyte on Ambertlite XAD-2, resin and subsequent elution, clean-up and HPLC fraction of the extract. The concentrations of DDTs, HCBs, HCHs, CHLs and PCBs in the Vistula River water ranged between 120-840, 7.6-52, 1600-410,000, 8.1-57 and 120-300 pg/l, respectively. During 12 months period of the study the total load of DDTs, HCBz, HCHs, CHLs and PCBs transported with the Vistula River water to the Gulf of Gdańsk was assessed on 10.54, 0.73, 1377, 0.38 and 5.02 kg, respectively.

Scopus

PubMed

researchmap

The concentrations of organochlorine pesticides such as DDTs, HCHs, CHLs, HCB and polychlorinated biphenyls (PCBs) were determined in ambient are samples collected in city of Gdańsk in 1991-1992 to understand concentrations, sources and seasonal distribution. Polyurethane foam plugs were used as adsorbents for collection of persitent organochlorines in ambient air samples. Identification and quantification of organochlorines were carried out using a capillary column gas chromatography and ECD (63Ni) detection. HCB, alpha-HCH, gamma-HCH, p,p&#039;-DDT, o,p&#039;-DDT, p,p&#039;-DDE, o,p&#039;-DDE, p,p&#039;-DDD, o,p&#039;-DDD and PCBs were detected in all samples, while the constituents of technical chlordan were absent in concentration above the detection limit of the method (trans-chlordane &lt; 14 pg/m3, cis-chlordane &lt; 8.1 pg/m3 and trans-nonachlor &lt; 7.4 pg/m3). The concentrations of HCB and PCBs were depended on the air temperatures, hence their main source can be related to a process of degasing from the soil.

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：HOKKAIDO UNIV  

To investigate the effect of the environmental pollutants, polycyclic aromatic hydrocarbons (PAHs), on retinoic acid-induced teratogenesis, all-trans-retinoic acid (RA) dissolved in corn oil (120 mg/kg) was administered orally to pregnant rats at the 11th day of gestation with and without the prior intraperitoneal treatment with 10 mg/kg 3-methylcholanthrene (3-MC) for 3 days. Darns were killed on the 20th. day of pregnancy. The examinations of fetuses revealed that 3-MC barely enough to cause induction of P-450 in pregnant dams had profound embryo-toxic effects : the fetal resorption amounted to similar to 60% of total number of implantations. The fetuses survived weighed less than the control fetuses. All of RA-treated mothers had fetuses with abnormalities, and the main malformations were: absence of tail (100%), caudal and sacral malformations (100%), and cleft palate (42%). Pregnant dams received both 3-MC and RA had a reduced severeness of tail anomaly (33%), while the rest, 67%, had short vestigial tail. Caudal and sacral malformations were detected but at a milder degree. We did not observe cleft palate in this group. The concurrent treatment of dams with 3-MC and RA led to an increased inducibility of cytochrome P-450 and subsequently, CYP1A1 dependent enzyme activity higher than those observed after the injection of 3-MC alone. UDP-glucuronyl-transferase activity was also markedly induced in concurrent 3-MC and RA group higher than that in 3-MC alone. We suggest that the induction of P-450 and alteration of metabolic enzyme activities may play an important role in reducing the teratogenic potency of RA. However, RA-treatment did not retard the embryo-toxic effect of 3-MC but rather potentiated.

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

Concentrations of lead, mercury, and cadmium in the liver, kidney, and muscle of four Steller&apos;s sea eagles (Haliaeetus pelagicus) and one white-tailed sea eagle (Haliaeetus albicilla) that were found dead or debilitated and subsequently died in Hokkaido, Japan, from 1986 to 1997 were determined. High lead concentrations (&gt;70 mu g/g dry weight) were detected in the liver of two Steller&apos;s sea eagles and the white-tailed sea eagle. Lead shot was also found in the intestine and gizzard of one Steller&apos;s sea eagle and the white-tailed sea eagle, respectively. Mercury and cadmium concentrations in the tissues of these raptors were low, implying that the toxicities of these elements were negligible. These results indicate that eagles in Hokkaido are suffering from secondary poisoning through ingestion of lead shot embedded in the tissue of their prey.

DOI： 10.1897/1551-5028(1999)018<0448:PSOLPO>2.3.CO;2

Web of Science

Scopus

researchmap

To investigate the effect of the environmental pollutants, polycyclic aromatic hydrocarbons (PAHs), on retinoic acid-induced teratogenesis, all-trans-retinoic acid (RA) dissolved in corn oil (120 mg/kg) was administered orally to pregnant rats at the 11th day of gestation with and without the prior intraperitoneal treatment with 10 mg/kg 3-methylcholanthrene (3-MC) for 3 days. Dams were killed on the 20th day of pregnancy. The examinations of fetuses revealed that 3-MC barely enough to cause induction of P-450 in pregnant dams had profound embryo-toxic effects: the fetal resorption amounted to∼60% of total number of implantations. The fetuses survived weighed less than the control fetuses. All of RA-treated mothers had fetuses with abnormalities, and the main malformations were absence of tail (100%), caudal and sacral malformations (100%), and cleft palate (42%). Pregnant dams received both 3-MC and RA had a reduced severeness of tail anomaly (33%), while the rest, 67%, had short vestigial tail. Caudal and sacral malformations were detected but at a milder degree. We did not observe cleft palate in this group. The concurrent treatment of dams with 3-MC and RA led to an increased inducibility of cytochrome P-450 and subsequently, CYP1A1 dependent enzyme activity higher than those observed after the injection of 3-MC alone. UDP-glucuronyl-transferase activity was also markedly induced in concurrent 3-MC and RA group higher than that in 3-MC alone. We suggest that the induction of P-450 and alteration of metabolic enzyme activities may play an important role in reducing the teratogenic potency of RA. However, RA-treatment did not retard the embryo-toxic effect of 3-MC but rather potentiated.

Scopus

researchmap

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Taylor and Francis Ltd  

1. The present authors have previously developed a transgenic rat carrying a chimeric gene of the mouse whey acidic protein promoter and the structural portion of human growth hormone (GH) gene. Among this (hGH-TG) rat, a line (low GH rat) missing a male-specific pulsatile GH secretary pattern due to suppression of endogenous GH secretion and having a continuous low GH (hGH and rat GH) level in the peripheral circulation was identified. The latter rat was also characterized as having severe obesity with age. This strain (low Gh rat) was used to correlate the sex-specific secretory pattern of GH with the sex-specific expression of cytochrome P450 (CYP) in rat. 2. Comparisons were made between the low GH rat and the non-transgenic rat as to the expression of liver microsomal CYP isozymes. The following enzyme activities were assessed: testosterone (T) hydroxylation and oxidation
ethoxyresorufin O-dealkylation (EROD)
bunitrolol (BTL) 4-hydroxylation and T5 α-reduction. Protein expression of CYP1A, CYP2C11, CYP2D, CYP2E1, CYP3A2 and CYP4A1 were also assessed by Western blot analysis. 3. Enzyme activities and protein expression of CYP2C11 (T16 α and 2α-hydroxylase and 17-oxidase activities) and CYP3A2 (T6β and 2β-hydroxylase activities) levels, which are known to be higher in the male than in the female rat, were significantly lower in the adult male low GM rat than in the control male rat. In contrast, CYP2A1 (T7 α-hydroxylase) and T5-α-reductase activities, which are known to be specifically elevated in the female, were significantly higher in the adult male low GH rat than in the control male rat. Thus, the loss of male-specific secretory pattern of GH results in feminization of the pattern of expression of CYP and T5 α-reductase activity in the liver. 4. In contrast to other GH-deficient models so far studied, an increase in CYP4A1 and a decrease in CYP2E1 protein expression were observed in the low GH rat. These trends are consistent with the characteristic phenotype of obesity in the transgenic rat because CYP4A1 and CYP2E1 enhance fatty acid excretion and glyconeogenesis from fatty acids respectively.

DOI： 10.1080/004982599237886

Scopus

PubMed

researchmap

researchmap

Language：English   Publisher：AMER CHEMICAL SOC  

DOI： 10.1021/es980216p

Web of Science

Scopus

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

The hepatopancreases of freshwater crabs (Eriocheir japonicus) collected from three Japanese rivers (Barato, Shiribetsu, and Tone) were analyzed for planar halogenated aromatic hydrocarbons (HAHs), including polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), and coplanar polychlorinated biphenyls (PCBs). The hepatic glutathione S-transferase (GST)dependent enzyme activities in the crab hepatopancreas were also measured to examine their potential as biomarkers for the contaminants. Crabs from the Tone River, which runs through industrial, agricultural, and urban areas, have the highest concentrations of HAHs (4,100 pg/g fat weight), followed by those from the Barato River (2,430-2,970 pg/g fat weight), whereas crabs from the Shiribetsu River were relatively less contaminated (1,350-1,800 pg/g fat weight). Identification of numerous PCDD and PCDF congeners in crabs from all three rivers provided evidence that one of the major sources of PCDDs and PCDFs was waste incineration. In addition, crabs from the Barato and Shiribetsu Rivers were notably contaminated with 1,3,6,8- and 1,3,7,9-TeCDD congeners, which suggests that a possible source was chlornitrofen, which has been extensively used in paddy fields as a herbicide. Calculation of 2,3,7,8-tetrachlorinated dibenzo-p-dioxin toxic equivalents (TEQs) showed that the causal contaminants of higher TEQs in crabs from the Tone River (94.7 TEQ picograms per gram fat weight) were PCDDs and PCDFs, although the most important contributor to the total TEQs was coplanar PCBs (49.95%). The crab hepatopancreas appeared to have abilities to transfer glutathione to 1-chloro-2,4-nitrobenzene (CDNB) and 3,4-dichloronitrobenzene (DCNB). The crabs with the highest TEQ levels showed the highest GST activities. The current results and our previous data lead us to conclude that cytochrome P450 and GST-dependent enzyme activities (benzo[a]pyrene hydroxylation and CDNB and DCNB conjugation) in freshwater crab hepatopancreases are likely to be useful biomarkers for the contamination of planar aromatic hydrocarbons such as benzo[a]pyrene, PCDDs, PCDFs, and coplanar PCBs.

DOI： 10.1897/1551-5028(1998)017<1490:AOHAHA>2.3.CO;2

Web of Science

Scopus

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

Tissues of northern fur seals (Callorhinus ursinus) from the Pacific coast of Japan and double-crested cormorants (Phalacrocorax auritus) from the Great Lakes were analyzed in order to explore the enantioselective accumulation of alpha-hexachlorocyclohexane (HCH). The effects of biological and ecological factors such as species, tissue, sex, age, feeding habit, and habitat, which may be attributable to the differences in accumulation between enantiomers, were also investigated. The enantiomeric ratios (ERs) of (+)-/(-)-alpha-HCH in fat tissue of female fur seals, composed of different age groups, collected in 1986 (1.58 +/- 0.25) exhibited greater values than those in abiotic and lower trophic levels previously reported. No age trend of ERs was found in female northern fur seals. There appeared to be a temporal transition of ERs in adult female northern fur seals collected in 1971-1988. Regression analysis showed a significant relationship between ERs and feeding habits (p = 0.003). Analysis of breast muscle of double-crested cormorants exhibited no sex difference in ERs. ERs (1.26 +/- 0.13) in cormorants from Lake Michigan were significantly higher than those (1.01 +/- 0.18) from Lake Superior (p = 0.002), suggesting the effects of factors such as feeding habit and habitat. Enantiomeric accumulation in the body of double-crested cormorants was tissue-specific. No age trend of ERs was seen in breast muscle of cormorants. The result implies that sexual maturity, aging and breeding activities are less effective for changing ERs. The ERs in higher trophic animals could be influenced by species-specific metabolism and transport process in the body as biological factors and by feeding habit and habitat as ecological factors.

DOI： 10.1021/es980115r

Web of Science

Scopus

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

In order to understand the residue levels of organochlorine compounds (OCs) and their accumulation patterns in wildlife inhabiting Chubu region, Japan, the concentrations of polychlorinated biphenyls (PCBs), hexachlorocyclohexane isomers (HCHs), DDT compounds (DDTs) and hexachlorobenzene (HCB) were measured in 8 species of terrestrial mammals and 10 species of birds. In view of feeding habits, the contamination levels of OCs were found to be higher in omnivorous mammals than in herbivorous ones, and in fish-eating ones and raptores than in omnivorous birds. In fox and dog, PCB 180 (2, 2', 3, 4, 4', 5, 5'-heptachlorobiphenyl) was the most dominant PCB congener, while in the other species PCB-153 (2, 2', 3, 4', 5, 5'-hexachlorobiphenyl) was the most persistent. The ratios of lower chlorinated PCB congeners (tri- to tetra-) to total PCBs were larger in fish-eating birds than in the other birds. The results indicate that the compositions of PCB congeners would reflect the differences of feeding habits and xenobiotic metabolizing systems among each species. (C) 1998 Elsevier Science Ltd. All rights reserved.

DOI： 10.1016/S0045-6535(98)00011-3

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：OXFORD UNIV PRESS  

Dog CYP2D15 was expressed in Sf9 cells with a recombinant baculovirus. Infection of Sf9 insect cells with a recombinant dog CYP2D15-virus resulted in the expression of a protein which cross-reacted with a polyclonal antibody against a dog CYP2D15-specific peptide, The difference spectrum of CO-complex of reduced P450 of the infected cell microsomes had a maximal absorbance at 449 nm, The specific content of P450 was calculated to be 0.56 nmol/mg of Sf9 cell microsomal protein, Although the expressed dog CYP2D15 showed high catalytic activity for the hydroxylations of bunitrolol and imipramine at low substrate concentration (10 mu M), the catalytic activity for that of debrisoquine (50 mu M) was extremely low as compared with that of CYP2D from other species, Dog liver microsomes also showed bunitrolol and imipramine hydroxylase activities, but not debrisoquine hydroxylase activity at the same substrate concentrations, In addition, the expressed CYP2D showed high catalytic activity for imipramine N-demethylation, Thus, our study reveals that the expressed dog CYP2D15 engages in high catalytic activity and has a unique substrate specificity from other CYP2D subfamilies, Western blot analysis suggested that the dog CYP2D15 contents were less than 4% of the total liver P450 content, assuming that 100% of expressed CYP2D15 incorporated heme.

DOI： 10.1093/oxfordjournals.jbchem.a021905

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

Hepatic butyltin concentrations were determined in 63 cetaceans belonging to 14 species and four pinnipeds belonging to two species collected from North Pacific and Asian coastal waters. Butyltin compounds (BTs) including tributyltin (TBT), dibutyltin (DBT), and monobutyltin (MET) were detected in almost all the liver samples suggestive of its worldwide distribution. The elevated residues detected in coastal species and low concentrations found in off-shore species indicate a high degree of butyltin contamination in coastal waters than in the open sea. Mammals inhabiting waters of developed nations were found to contain higher BT concentrations compared with those collected from the waters proximal to developing countries. These observations strongly suggest serious BT contamination in the waters of developed countries than in developing nations at present. Among the samples collected off Japanese coastal waters, lower BT concentrations were found in pinnipeds compared with the cetaceans, suggestive of a possible difference in degradation capacities and excretory moulting between these two groups of animals. The estimated concentration ratio of BT in the liver of killer whale fetus to its pregnant mother was relatively low (0.015), indicative that transplacental transfer of BTs from the mother to her fetus is a deal less. Among the BT breakdown products, DBT was predominant in most of the liver samples analyzed, followed by TBT and MBT.

DOI： 10.1021/es970543h

Web of Science

Scopus

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

The Dark Agouti rat has been proposed as a model for the human debrisoquine 4-hydroxylase polymorphism. Earlier studies suggested that the poor metabolizer phenotype in the Dark Agouti rat is caused by the absence of the expression of CYP2D1 mRNA. Although CYP2D1 is the major enzyme catalyzing debrisoquine 4-hydroxylation, other reports have indicated the involvement of a CYP2D purified from rat hepatic microsomes and presumed to be CYP2D2, which also exhibits this activity. The levels of CYP2D1 and CYP2D2 mRNAs were markedly lower in Dark Agouti as compared to Sprague Dawley rats. Using a baculovirus expression system, recombinant CYP2D1 and CYP2D2 from Spodoptera frugiperda insect cells were examined and were found to both forms catalize debrisoquine 4-hydroxylase activity. These results suggest that reduced debrisoquine 4-hydroxylase activity in the Dark Agouti rat is caused by the low level expression not only of CYP2D1, but also of CYP2D2. Interestingly, bunitrolol 4-hydroxylation was catalyzed by recombinant CYP2D2, while CYP2D1 was inactive toward this substrate. Thus, the low bunitrolol 4-hydroxylation in Dark Agouti rats was caused by the low level of CYP2D2 expression in this rat strain.

DOI： 10.1097/00008571-199802000-00010

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Oxford University Press  

We have studied the regio- and stereoselectivity of ring-hydroxylation and N-desisopropylation of S(-)- and R(+)-propranolol, using dog liver microsomes and the expressed dog CYP2D15 in insect cells. In dog liver microsomes, 4-hydroxylation was the preferred pathway in S(-)-propranolol oxidation, while N-desisopropylation was the preferred pathway in R(+)-propranolol oxidation. S(-)-Propranolol was preferred over R(+)-propranolol as substrate for 4- and 5-hydroxylations, while R(+)-propranolol was the preferred substrate for N-desisopropylation at higher substrate concentrations. The expressed CYP2D15 had high catalytic activities toward 4-, 5-hydroxylation, as well as N-desisoprspylation of both enantiomers. At the substrate concentrations used, 4-hydroxylation was the preferred pathway for the metabolism of both enantiomers, and S(-)-propranolol was the preferred substrate over R(+)-propranolol for all three monooxygenations catalyzed by CYP2D15. Anti-CYP2D15 peptide antibody strongly inhibited 4- and 5-hydroxylation of both enantiomers in dog liver microsomes, while it did not inhibit their N-desisopropylation. These findings suggest that CYP2D15 is highly responsible for the stereoselective 4- and 5-hydroxylations of propranolol in dog liver microsomes.

DOI： 10.1093/oxfordjournals.jbchem.a022000

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Taylor and Francis Ltd  

1. The herbicides butachlor (2-chloro-2',6',diethyl-N-[buthoxymethyl acetanilide) and pretilachlor (2-chloro-2',6'-diethyl-N-[2-propoxyethyl] acetanilide) are widely used in Asia, South America, Europe and Africa. Isoprothioiane (diisopropyl-1,3-dithiolan-2-ylidenemalonate) is used as a fungicide and an insecticide in rice paddies. We administered these agrochemicals to the male rat and examined their effects on cytochrome P450 (P450), glutathione S-transferase (GST), UDP-glucuronosyltransferase (UDPGT), and NAD(P)H-quinone oxidoreductase 1 (NQO1)-related metabolism in the liver. 2. Administration of isoprothiolane, butachlor or pretilachlor to rat induced hepatic P4502B subfamily-dependent enzyme activities (pentoxyresorufin O-depentylation and testosterone 16 β-hydroxylation) up to 271-413% of control, which coincided with the increase in expression levels of the P4502B apoprotein. 3. Activities of GST toward 1-chloro-2,4-nitrobenzene and 3,4-dichloronitrobenzene were slightly induced (127-133% of control) in the liver of the rat treated with these pesticides. On the other hand, marked elevations of UDPGT activities toward p-nitrophenol (164-281% of control) were observed. NQO1-related metabolism (menadione reductase activity) was also induced (123-176% of control) in the liver of rat treated with these agrochemicals. 4. These results indicate that some of the agrochemicals currently in use are capable of inducing phase I and II xenobiotic-metabolizing enzyme activities in an isozyme selective manner. The induction of these activities may disrupt normal physiologic functions related to these enzymes in exposed animals.

DOI： 10.1080/004982598238921

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：TAYLOR & FRANCIS LTD  

1. During liver regeneration in the male rat, the metabolic activities of imipramine were differentially affected depending on the specific metabolic pathways. Imipramine N-demethylation was markedly reduced whereas 2-hydroxylation showed only a moderate reduction following partial hepatectomy.
2. A slight decline was observed in the hepatic microsomal content of CYP2D apoprotein, whereas a substantial decrease occurred in CYP2C11 content during liver regeneration. Since imipramine 2-hydroxylation and N-demethylation are mediated by CYP2D and 2C11 respectively, metabolic pathway-specific alterations in the activities of imipramine metabolism are explained by the isozyme selective alteration in the levels of CYPs in regenerating liver.
3. No significant effect of regeneration was observed on expression of CYP2B1 and 2E1 apoproteins. CYP3A2 apoprotein, one of the male-specific CYP isoforms, was significantly suppressed in regenerating liner showing a similar pattern of alteration to the levels of CYP2C11. The alteration pattern of the CYP1A1 level was different to the above with a moderate decline at the first day post-operation and a marked rebound thereafter.
4. In the partially hepatectomized male rat, no significant increase in androstenedione 5-alpha reductase activity, an activity predominant in the female rat, was detected. It is concluded that the pattern of alterations of hepatic oxidative metabolism during liver regeneration was not related to the functional feminization of the liver.

DOI： 10.1080/004982597240091

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCI LTD  

Concentrations of butyltin compounds were determined in the kidney and liver of various seabirds collected from Japan, Korea, the North Pacific Ocean and the southern Indian Ocean. These compounds were detected in most of the samples, which indicated widespread contamination in higher trophic aquatic animals even in remote areas. The highest mean residue concentrations of butyltins in the kidney (300 ng/g wet wt) and liver (280 ng/g wet wt) were in common cormorants from Lake Biwa, Japan. Laysan albatross from the North Pacific Ocean accumulated higher butyltin residues in the liver (43 ng/g wet wt) among open-ocean birds. Even though the number of samples analysed was small, it can be suggested that birds inhabiting inland to coastal areas had higher exposure to butyltins than those in the ocean. To our knowledge, this is the first study reporting on butyltin pollution in seabirds in global terms. (C) 1997 Elsevier Science Ltd.

DOI： 10.1016/S0141-1136(97)00001-9

Web of Science

Scopus

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：John Wiley and Sons Ltd  

Although organotins are notorious man-made organometallic species introduced into the aquatic environment, no investigation had been concerned with contamination of higher trophic animals such as marine mammals until the last few years. Our recent work demonstrated the detection of butyltin compounds (BTCs), including mono- (MBT), di-(DBT), and tri-butyltin (TBT) in marine mammals. This paper reviews BTC contamination in higher trophic animals, based on our recent publications. Analysis for BTCs showed significant accumulation in tissues and organs of three unless porpoises (Neophocaena phocaenoides) collected from Japanese coastal waters. More than 10 μg of butyltin ions per gram on a wet weight basis were detected in the liver of a porpoise collected in the semi-closed sea. Distribution of BTCs in the tissues and organs of the porpoises showed a similar pattern to several other marine mammal species: higher concentrations in liver and kidney, and lower in muscle and blubber. In addition, tissues and organs from two water birds and one sea turtle species were also analyzed for BTCs, and their concentrations and compositions were compared among the species. The results showed that the distribution of these contaminants extends widely, not only to marine mammals but also to other higher trophic species. On the other hand, the composition of the BTCs exhibited a specific profile in each species. The ratios of hepatic concentrations of DBT or MBT to TBT for marine mammals were relatively lower than those of water birds and the sea turtle, indicating that metabolism and excretion of TBT may be less efficient in the mammalian species. © 1997 by John Wiley &amp
Sons, Ltd.

DOI： 10.1002/(SICI)1099-0739(199704)11:4<257::AID-AOC575>3.0.CO;2-2

Scopus

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER VERLAG  

Concentrations of butyltin compounds (BTs) were determined in various body tissues of common cormorants (Phalacrocorax carbo) collected from the Lake Biwa, Japan. Elevated concentrations of butyltins were detected in the feathers of cormorants. Among other organs and tissues, butyltin levels were also higher in the kidney (290 +/- 150 ng/g) and liver (270 +/- 260 ng/g), ranging from 115 to 544 ng/g and 142 to 1007 ng/g (wet wt basis), respectively. The accumulation of BTs in cormorant bodies was in the order of MBT &gt; DBT &gt; TBT and their organ specific burdens were in the order of muscle greater than or equal to feathers &gt; skin &gt; liver &gt; rest of the tissues and organs. The higher levels of BTs residues in feather suggested the excretion of about one fourth of their body burden during a complete molting cycle, which has been a natural detoxification mechanism in these birds. Based on the whole body concentrations of BTs in cormorants (42-160 ng/g wet wt) and fish (10-55 ng/g wet wt) biomagnification factors were assessed to be in the range of 1.1-4.1. To our knowledge, this is the first fundamental study to substantially indicate the contamination and kinetics of BTs in wild birds.

DOI： 10.1007/s002449900100

Web of Science

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

The enantiomeric ratio of alpha-hexachlorocyclohexane (alpha-HCH) in blubber of 10 species of adult male small cetaceans has been determined by means of capillary gas chromatography using beta-cyclodextrin as a chiral stationary phase. The enantiomeric ratio of (+)-alpha-HCH/(-)-alpha-HCH ranged from 1.6 to 2.8, showing diverse values. Moreover, even in the same species, the ratios varied between animals collected from different localities. Dall's porpoise (Phocoenoides dalli) collected from the Bering Sea had enantiomeric ratios of 2.0-2.1 and others, from the North Pacific and Japan Sea, exhibited ratios ranging from 1.6-1.9. The ratios of beta-HCH concentration to total HCH concentration (beta-HCH/Sigma HCH) was linearly related to the enantiomeric ratios of alpha-HCH (r=-0.46, p&lt;0.005). This may indicate that the metabolic capacity to degrade HCH isomers among cetaceans can be evaluated in terms of degradation of the (+)-alpha-HCH enantiomer. Present enantiomeric ratios were compared with earlier observations on various environmental samples and unbalanced degradation of (+)- and(-)-alpha-HCH enantiomers was suggested in small cetaceans.

DOI： 10.1016/0025-326X(95)00105-V

Web of Science

Scopus

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer New York LLC  

Concentrations of butyltin compounds (BTs) were determined in various body tissues of common cormorants (Phalacrocorax carbo) collected from the Lake Biwa, Japan. Elevated concentrations of butyltins were detected in the feathers of cormorants. Among other organs and tissues, butyltin levels were also higher in the kidney (290 ± 150 ng/g) and liver (270 ± 260 ng/g), ranging from 115 to 544 ng/g and 142 to 1007 ng/g (wet wt basis), respectively. The accumulation of BTs in cormorant bodies was in the order of MBT &gt
DBT &gt
TBT and their organ specific burdens were in the order of muscle ≤ feathers &gt
skin &gt
liver &gt
rest of the tissues and organs. The higher levels of BTs residues in feather suggested the excretion of about one fourth of their body burden during a complete molting cycle, which has been a natural detoxification mechanism in these birds. Based on the whole body concentrations of BTs in cormorants (42-160 ng/g wet wt) and fish (10-55 ng/g wet wt) biomagnification factors were assessed to be in the range of 1.1- 4.1. To our knowledge, this is the first fundamental study to substantially indicate the contamination and kinetics of BTs in wild birds.

DOI： 10.1007/BF00212368

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier Ltd  

The present study was conducted to elucidate the specific distribution of butyltin (BT) compounds in various tissues and organs of Steller sea lions collected from coastal waters of Hokkaido, Japan. BT concentrations were an order of magnitude higher in the liver than in other tissues and organs except hair, whereas organochlorine (OC) compounds accumulated at two to three orders of magnitude higher in blubber than in other tissues. No relationship was observed between BT concentrations and the lipid content in tissues, while the levels of OCs were positively associated with the lipid content. The levels of BTs in hair (1500 ng g-1 on a wet weight basis) were the highest of all the tissues analysed. Results also suggested that 26% of the total BT burden in the body was eliminated through shedding. Selective accumulation of BTs in liver and hair is attributed to its protein-binding capacity rather than lipophilicity. The discovery of high concentrations of BTs in hair implies their excretion by shedding in piliferous animals.

DOI： 10.1016/0025-326X(96)84576-0

Scopus

researchmap

DOI： 10.1021/es00003a030

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER VERLAG  

Concentrations of heavy metals, organochlorine pesticides, polychlorinated biphenyls and organotins were determined in horseshoe crabs, Tachypleus tridentatus, collected from Japanese coastal waters. Heavy metal concentrations were high in the hepatopancreas, gill and egg. Residue levels of heavy metals were comparable to those recorded in most benthic organisms from Japanese coastal waters. Organochlorine concentrations were detected at a few ng/g acid the residue pattern followed the order of polychlorinated biphenyls (PCBs) &gt; chlordane compounds (CHLs) &gt; hexachlorocyclohexanes (HCHs) &gt; dichlorodiphenyltrichloroethane (DDTs) &gt; hexachlorobenzene (HCB). Butyltin concentrations were high in the hepatopancreas, ranging from 350-2,270 ng/g in Hakata Bay and 570-5,000 ng/g (on a wet wt basis) in Habu Bay. Elevated concentrations of butyltins were also detected in the eggs of horseshoe crabs. High accumulations of butyltins in horseshoe crabs may pose a serious threat to their survival and therefore needs immediate attention to prevent their extinction.

DOI： 10.1007/BF00213967

Web of Science

Scopus

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCI LTD  

Concentrations of butyltin residues were determined in muscle tissue of fish collected from local markets and sea food shops in India, Bangladesh, Thailand, Indonesia, Vietnam, Taiwan, Australia, Papua New Guinea and the Solomon Islands. Contamination levels were determined in the Asia-Pacific region and human exposure was estimated. Similarly, corresponding liver samples of fish muscle collected in Australia, Papua New Guinea and the Solomon Islands were analyzed to obtain information on partitioning of butyltin compounds between muscle and liver tissues. Butyltin compounds were detected in most of the samples which suggested widespread contamination in Asia and Oceania. The concentrations of butyltin compounds were, on average, an order of magnitude higher in liver than in muscle. Residue concentration of Sigma butyltin in liver was found to be correlated significantly (p &lt; 0.02) with those in muscle. Intensive ship-scrapping activities, sewage disposal and antifouling paints are considered the major sources of butyltins in this region. Increased proportions of MBT over DBT and TBT in samples from most locations indicated degradation of TBT to MBT in fish tissues during storage at 4 degrees C in the dark over 1-2 years. The possibility that fish have been subject to increased exposure to MBT and that TBT degrades to MBT quite rapidly in tropical environments are also considered. Butyltin concentrations in fish from Asia and Oceania were lower than those reported for Japan, Canada and the USA. Although the number of samples analyzed from each country was small, it is tentatively suggested that intake of butyltins by humans via consumption of fish in these countries was &lt; 25% of the tolerable daily intake of 250 ng kg bw(-1) day(-1). To our knowledge, this is the first study reporting on butyltin pollution in developing Asian countries.

DOI： 10.1016/0269-7491(95)00028-P

Web of Science

Scopus

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Organotins are one of the most toxic chemicals in the aquatic environment. While contamination and toxic effects of organotin compounds in lower trophic aquatic organisms have been well-documented, no investigation has focused so far on higher aquatic organisms like marine mammals. We attempted to analyze butyltin compounds (BTCs), including mono-(MBTs), di-(DBTs), and tributyltin compounds (TBTs), in various tissues and organs of finless porpoise (Neophocaena phocaenoides) collected from Japanese coastal waters and detected these compounds in all the animals. The highest residue levels were found in the liver of a porpoise collected in the inland sea, recording more than 10 ppm BTCs on a wet weight basis. The composition of BTCs was different according to the tissues and organs with higher proportions of DBTs noticed in the liver and blood. Estimation of BTC burdens in tissues and organs indicated that muscle, liver, and blubber retained predominant portion of TBTs, DBTs, and MBTs. The occurrence of higher rates of TBTs on the whole implied the lower metabolic potential of porpoises to BTCs. © 1995, American Chemical Society. All rights reserved.

DOI： 10.1021/es00012a011

Scopus

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Contamination of semivolatile organochlorines (OCs) such as hexachlorobenzene (HCB), hexachlorocyclohexanes (HCHs), DDTs, chlordanes, and polychlorinated biphenyls (PCBs) was assessed in air, water, sediments, and soils from the Lake Baikal region, Russia. Comparison of the residue levels in the lake with those in other regions suggested the presence of local sources of DDTs and PCBs, although the residues were considered to be lower than those in the low-latitude areas in the eastern Asia and Oceania. Larger proportions of p,p'-DDT to total DDTs and similarities of PCB congener compositions to a Russian technical PCB formation were found in the samples analyzed, implying their usages nearby the lake. The estimated fluxes of OCs by gas exchange across the air-water interface applying the twofilm model indicated that the lake water plays a role as a sink for HCB, HCHs, and DDTs and also serves as a source for PCBs. The magnitude for PCB volatilization in this lake was found to be smaller than those in the Great Lakes for which the values have been previously reported. © 1995, American Chemical Society. All rights reserved.

DOI： 10.1021/es00003a030

Scopus

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE BV  

The present paper overviews the global contamination by persistent organochlorines and their ecotoxicological implications on marine mammals. The recent pattern of contamination by organochlorine residues in the coastal environment is prominent in tropical regions due to continuous usage in the low-latitude developing countries. The major emission source of organochlorines is probably the tropical belt and large quantities of volatilized contaminants are dispersed through the atmosphere on global terms. Reflecting this, a considerable contamination was observed in open ocean tropical waters as well as in the Arctic and nearby waters. The study of the mass transfer of organochlorines at the air-water interface suggests that the oceanic water bodies, particularly Arctic waters, act as a sink for persistent contaminants. In this regard, the marine mammals, particularly cetaceans, are one of the animal groups receiving high concentrations of persistent organochlorines arising out of a worldwide contamination. They can amplify much greater amounts of toxic contaminants through feeding and also pass them in large quantities from one generation to the next through lactation. Unfortunately, these animals have a smaller capacity for degradation of these contaminants due to the specific mode of cytochrome P-450 enzyme systems. These drug-metabolizing enzyme systems may be related to the possible effects of persistent organochlorines, particularly coplanar PCBs. Furthermore, the residue levels of these contaminants in marine mammals are unlikely to decline in the near future. Considering all these facts, it may be concluded that marine mammals are one of the most vulnerable and possible target organisms with regard to long-term toxicity of hazardous man-made chemicals in the future.

DOI： 10.1016/0048-9697(94)90086-8

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

The blubber samples of eight species (12 specimens) of marine mammals caught between 1981 and 1993 in seas surrounding Japan and in the Indian, North Pacific and Antarctic Oceans, were analysed for butyltin compounds (BTCs). The column chromatography using dry florisil and acetonitrile enabled isolation of BTCs from lipids in fatty tissues like blubber, and led to the reliable analysis with efficient recoveries for these contaminants. BTCs were detected in all the animals except a minke whale from the Antarctic Ocean. The highest residue levels were found in a finless porpoise from the Seto-inland Sea, Japan with a BTC concentration of 770 ng g-1 on wet wt basis. Geographical distribution of the BTC concentrations in marine mammals showed a decreasing trend from the coastal to the open seas, indicating the presence of larger pollution sources nearby the coastal regions. Compositions of the BTCs in the blubber of finless porpoises seemed to be different from those found in aquatic organisms of lower trophic levels. Lower contributions of dibutyltins to the total BTCs in the blubber suggest the presence of their specific metabolic pathways. To our knowledge, this is the first report on the detection of BTCs in marine mammals. © 1994.

DOI： 10.1016/0025-326X(94)90362-X

Scopus

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Three surface sediments and two sediment cores were collected from the Gulf of Alaska, Bering Sea and Chukchi Sea, and analysed for persistent organochlorines (OCs). The geographical distributions of OCs showed different patterns according to their physicochemical properties. The concentrations of HCHs and HCB revealed rather uniform distribution, suggesting their more transportable nature in long-range atmospheric transport. On the other hand, DDTs and PCBs were predicted to be less transportable via the atmosphere due to the decreasing trends of residue levels in sediments from south to north. The OC profiles in the sediment core from the Gulf of Alaska which seemed to be preserved without turbation revealed the elevated residue levels from bottom to surface layers. This implies that the aerial inputs of OCs in the cold ocean are still continuing significantly. The accumulation rates of OCs into sediments were rather smaller than the atmospheric inputs, indicating that the residue levels in water bodies are unlikely to decrease rapidly in the near future. © 1994.

DOI： 10.1016/0025-326X(94)90334-4

Scopus

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCI LTD  

Persistent organochlorines in air, river water and sediment samples were analysed from eastern and southern Asia (India, Thailand, Vietnam, Malaysia, Indonesia) and Oceania (Papua New Guinea and Solomon Islands) to elucidate their geographical distribution in tropical environment. The concentrations of organochlorines in these abiotic samples collected from Taiwan, Japan and Australia were also monitored for comparison. Atmospheric and hydrospheric concentrations of HCHs (hexachlorocyclohexanes) and DDTs (DDT and its metabolites) in the tropical developing countries were apparently higher than those observed in the developed nations, suggesting extensive usage of these chemicals in the lower latitudes. CHLs (chlordane compounds) and PCBs (polychlorinated biphenyls) were also occasionally observed at higher levels in the tropics, implying that their usage area is also expanding southward. Distribution patterns of organochlorines in sediments showed smaller spatial variations on global terms, indicating that the chemicals released in the tropical environment are dispersed rapidly through air and water and retained less in sediments. The ratios of organochlorine concentrations in sediment and water phases were positively correlated with the latitude of sampling, suggesting that persistent and semivolatile compounds discharged in the tropics tend to be redistributed on a global scale.

DOI： 10.1016/0269-7491(94)90234-8

Web of Science

Scopus

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/0025-326X(93)90571-Z

Scopus

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Concentrations of organochiorines such as hexachlorocyclohexanes (HCHs), DDTs, chlordanes, and PCBs were determined in the air and surface water from various oceans in 1989–1990, for understanding their recent distribution and the role of ocean in the long-range atmospheric transport and fate on global terms. The atmospheric concentrations were found to be still higher in the Northern Hemisphere than in the Southern Hemisphere, although the distribution pattern suggested the shift or expansion of their major sources from the mid to low latitudes during the last decade. In surface water, HCHs showed a considerable contamination over 40° N, whereas DDTs were higher near tropical Asia. Chlordanes and PCBs exhibited rather uniform distributions in both the hemispheres. Estimations of fluxes by gas exchange across the air-water interface gave insight into the dispersal of organochiorines through oceanic atmosphere depending on their Henry's law constants and the tendency of more transportable ones to deposit into the cold waters as an ultimate sink. © 1993, American Chemical Society. All rights reserved.

DOI： 10.1021/es00043a007

Scopus

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

Water and sediment samples collected from the lower Chao Phraya River and a canal along the river during 1988 - 1991 were analyzed to determine the current status of contamination by organochlorine pesticides, such as HCHs, DDTs, aldrin, dieldrin and chlordanes. Aldrin and dieldrin had high frequencies of occurrence in water samples. The medians of concentrations of these pesticides were approximately one order of magnitude larger than total HCHs and total DDTs. Residue levels of these pesticides varied significantly. Relatively higher levels of aldrin were observed in the upstream; in contrast, residue levels of DDTs were higher in urban area. These phenomena seem to relate to the spraying purpose of these pesticides. Decreasing trends in the residue levels of pesticides during monitoring periods, however, were not observed clearly. Residue levels of organochlorines in the sediment samples were in the order of magnitude of PCBs, DDTs, chlordanes and HCHs.

Web of Science

Scopus

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：GORDON BREACH SCI PUBL LTD  

A HCH (BHC) application test was conducted in an experimental paddy field in the Vellar river watershed, Tamil Nadu state, South India. Interestingly, most of the HCH applied to the field was found to volatilize rapidly as low residue levels in water, rice plant and soil were recorded. After two weeks of an application, more than 90% of the HCH was found in the air and less than 10% in water, soil and rice plants, thus emphasizing that post-application volatilization is a major route for transport of insecticides to and through the atmosphere in tropical paddy areas. © 1991, Taylor &amp; Francis Group, LLC. All rights reserved.

DOI： 10.1080/03067319108232937

Web of Science

Scopus

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

The residue levels of the insecticide HCH in Vellar estuary, Tamil Nadu, South India were surveyed along with the physical structure of estuary and its hydrokinetic parameters to assess the transport of contaminants in tropical coastal areas. From the flux model it was estimated that most of the HCH applied to the catchment area of Vellar river is removed to the air and only a small part of it was drained to the sea. Compared to the present situation, the flux of HCH to the sea seems to be much larger in the past when the river structure was different from the present. This implies that at present the localized contamination of HCH in the sea is reducing: instead more rapid contamination is advancing on global terms due to the 'long-range atmospheric transport' of residues from the 'point-source' areas. © 1991.

DOI： 10.1016/0025-326X(91)90807-5

Scopus

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCI LTD  

Water samples collected from Vellar river and Pichavaran mangroves at Porto Novo (11° 29′ N, 79° 46′ E), Tamil Nadu State, South India, from December 1987 to January 1989 were analyzed to determine the seasonal variation of the levels of organochlorine insecticides such as HCH (BHC) and DDT. Both these insecticides showed higher levels from October to February, although this trend was more pronounced in HCH than DDT, reflecting the application of technical HCH largely and probably small quantities of DDT during the flowering season of rice. The α-HCH was detected as a dominant isomer for all seasons monitored followed by β-HCH Among DDT compounds, p, p′-DDT was the highest in river water except in the dry season when p,p′-DDD showed a higher percentage. On the other hand, in mangroves p,p′-DDE was highest during the wet season and p,p′-DDD during the dry season. Air-water partitioning data of HCH isomers and DDT compounds in Vellar river revealed that these chemicals tend to be in the water phase. These observations may aid in understanding the role of a tropical paddy area on the behavior and fate of man-made chemicals in view of worldwide contamination. © 1990.

DOI： 10.1016/0269-7491(90)90067-M

Web of Science

Scopus

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN SOC MECHANICAL ENGINEERS SANSHIN HOKUSEI BLDG  

Web of Science

researchmap

Interdisciplinary Studies on Environmental Chemistry, Vol. 3, Biological Responses to Chemical Contaminants: From Molecular to Community Level : Risk assessment of dioxins in wild birds by the combination of contamination level and species-specific response of aryl hydrocarbon receptor

researchmap

Interdisciplinary Studies on Environmental Chemistry Vol. 4, Environmental Specimen Bank: Exploring Possibility of Setting-up ESBs in Developing Countries : Molecular characterization of peroxisome proliferator-activated receptor isoforms from the baikal seal (Pusa sibirica)

researchmap

Interdisciplinary Studies on Environmental Chemistry Vol. 4, Environmental Specimen Bank: Exploring Possibility of Setting-up ESBs in Developing Countries : Toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on peripheral nervous system of developing red seabream (Pagrus major) embryos

researchmap

Interdisciplinary Studies on Environmental Chemistry Vol. 4, Environmental Specimen Bank: Exploring Possibility of Setting-up ESBs in Developing Countries : Development of an in vitro reporter gene assay for screening the ecdysone receptor agonists in mysid crustacean

researchmap

Interdisciplinary Studies on Environmental Chemistry Vol. 4, Environmental Specimen Bank: Exploring Possibility of Setting-up ESBs in Developing Countries : Development of an in vitro reporter gene assay for screening the ecdysone receptor agonists in mysid crustacean

researchmap

Interdisciplinary Studies on Environmental Chemistry Vol. 4, Environmental Specimen Bank: Exploring Possibility of Setting-up ESBs in Developing Countries : Molecular characterization of peroxisome proliferator-activated receptor isoforms from the baikal seal (Pusa sibirica)

researchmap

Interdisciplinary Studies on Environmental Chemistry Vol. 4, Environmental Specimen Bank: Exploring Possibility of Setting-up ESBs in Developing Countries : Toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on peripheral nervous system of developing red seabream (Pagrus major) embryos

researchmap

Interdisciplinary Studies on Environmental Chemistry vol. 3, Biological Responses to Contaminants: from Molecular to Community Level : Interindividual variation in arsenic metabolism in a Vietnamese population: association with 17 single nucleotide polymorphisms in AS3MT

researchmap

researchmap

Interdisciplinary Studies on Environmental Chemistry, Vol. 3, Biological Responses to Chemical Contaminants: From Molecular to Community Level : Risk assessment of dioxins in wild birds by the combination of contamination level and species-specific response of aryl hydrocarbon receptor

researchmap

researchmap

Interdisciplinary Studies on Environmental Chemistry vol. 3, Biological Responses to Contaminants: from Molecular to Community Level : Interindividual variation in arsenic metabolism in a Vietnamese population: association with 17 single nucleotide polymorphisms in AS3MT

researchmap