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Development of method for assessing species-specific risk of Ah receptor-mediated dioxin toxicity

Research Project

Project/Area Number 13480170
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field 環境影響評価(含放射線生物学)
Research InstitutionEhime University

Principal Investigator

IWATA Hisato  Ehime University, Center for Marine Environmental Studies, Professor, 沿岸環境科学研究センター, 教授 (10271652)

Co-Investigator(Kenkyū-buntansha) TANABE Shinsuke  Ehime University, Center for Marine Environmental Studies, Professor, 沿岸環境科学研究センター, 教授 (60116952)
Project Period (FY) 2001 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥6,300,000 (Direct Cost: ¥6,300,000)
Fiscal Year 2004: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2003: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2002: ¥2,500,000 (Direct Cost: ¥2,500,000)
Keywordsdioxin / Ah receptor / cormorant / albatross / red seabream / 水鳥 / ゼニガタアザラシ / バイカルアザラシ
Research Abstract

We identified two distinct AhR cDNAs (AhR1 and AhR2) from the livers of black-footed albatross (Diomedea nigripes) and common cormorant (Phalacrocorax carbo). The objective of this study is to investigate the functional characterization of the AhRs and their expression levels related to planar halogenated aromatic hydrocarbons (PHAHs) exposure and CYP1A expression in aquatic birds. In velocity sedimentation analysis using AhR proteins expressed by in vitro transcription and translation, both AhRs exhibited specific binding to [^3H]TCDD. Focusing on the amino acid residues corresponding to Ile^<325> and Ser^<381> in chicken AhR1, which may contribute to the differential TCDD-binding affinity, the amino acid residues in albatross and cormorant AhR1 were Ile-Ala and Val-Ala, respectively. The [^3H]TCDD binding affinity measured was in the order of chicken > albatross > cormorant, and agreed with the order that may be expected from the amino acids. In contrast, the binding affinity of avia … More n AhR2 appeared to be unrelated to the corresponding amino acids.
To investigate the molecular mechanism of TCDD toxicity in a marine fish species, red seabream (Pagrus major), we identified two distinct AHR isoform cDNAs (rsAHR1 and rsAHR2), which shared only 32% identity in full-length amino acid sequence. Quantitative analyses of both rsAHR mRNAs revealed that their tissue expression profiles were isoform-specific in different tissues of adult fishes ; rsAHR1 mRNA expressed primarily in brain, heart and ovary, while rsAHR2 mRNA was observed in all tissues examined. The expression of rsAHR1,rsAHR2 and CYP1A mRNAs were also determined in different developmental stages treated either with TCDD or solvent control at 10 hpf (hours post fertilization). Both rsAHR transcript levels increased prior to the stage at which heart beat and blood circulation were observable, but expression patterns were slightly different ; maximal expression of rsAHR1 and rsAHR2 mRNA were 96 hpf and 190 hpf, respectively. The rsAHR2 mRNA expression increased following TCDD exposure compared with solvent control, while TCDD did not affect the rsAHR1 mRNA level. Although basal expression of CYP1A mRNA was detectable, TCDD exposure further enhanced CYP1A mRNA level. The maximal expression of CYPIA mRNA was recorded before the onset of the first signs of TCDD toxicities such as yolk sac edema. Less

Report

(5 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (33 results)

All 2004 Other

All Journal Article (15 results) Publications (18 results)

  • [Journal Article] Searching for novel CYP members using cDNA library from a minke whale liver2004

    • Author(s)
      Kim, E.Y.
    • Journal Title

      Marine Environmental Research 58

      Pages: 495-498

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Identification of aryl hydrocarbon receptor 2 in aquatic birds : cDNA clonong of AHR1 and AHR2 and characteristics of their amino acid sequences2004

    • Author(s)
      Yasui, T.
    • Journal Title

      Marine Environmental Research 58

      Pages: 113-118

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Identification of constitutive androstane receptor cDNAs in northern fur seal(Callorhinus ursinus)2004

    • Author(s)
      Sakai, H.
    • Journal Title

      Marine Environmental Research 58

      Pages: 107-111

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Toxicokinetics of PCDD, PCDF and Coplanar PCB Congeners in Baikal Seal, Pusa sibirica : Age-related Accumulation, Maternal Transfer and Hepatic Sequestration2004

    • Author(s)
      Iwata, H.
    • Journal Title

      Environmental Science and Technology 38

      Pages: 3505-3513

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Levels and Toxicokinetic Behaviors of PCDD, PCDF and Coplanar PCB Congeners in Common Cormorants from the Lake Biwa, Japan2004

    • Author(s)
      Kubota, A.
    • Journal Title

      Environmental Science and Technology 38

      Pages: 3853-3859

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] バイカルアザラシCYP1A/1A2 cDNAの同定およびダイオキシン類蓄積濃度と各mRNA発現量の関係2004

    • Author(s)
      平川 周作
    • Journal Title

      環境毒性学会誌 7(2)

      Pages: 55-59

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Searching for novel CYP members using cDNA library from a minke whale liver.2004

    • Author(s)
      Kim, E.Y., Iwata, H., Fujise, Y., Tanabe, S.
    • Journal Title

      Marine Environmental Research 58

      Pages: 495-498

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Identification of aryl hydrocarbon receptor 2 in aquatic birds : cDNA clonong of AHR1 and AHR2 and characteristics of their amino acid sequences.2004

    • Author(s)
      Yasui, T., Kim, E.Y., Iwata, H., Tanabe, S.
    • Journal Title

      Marine Environmental Research 58

      Pages: 113-118

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Identification of constitutive androstane receptor cDNAs in northern fur seal (Callorhinus ursinus).2004

    • Author(s)
      Sakai, H., Iwata, H., Kim E.Y., Tanabe, S., Baba, N.
    • Journal Title

      Marine Environmental Research 58

      Pages: 107-111

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Toxicokinetics of PCDD, PCDF and Coplanar PCB Congeners in Baikal Seal, Pusa sibirica : Age-related Accumulation, Maternal Transfer and Hepatic Sequestration.2004

    • Author(s)
      Iwata, H., Watanabe, M., Okajima, Y.., Tanabe, S., Amano, M., Miyazaki, N., Petrov, E.A.
    • Journal Title

      Environmental Science and Technology 38

      Pages: 3505-3513

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Levels and Toxicokinetic Behaviors of PCDD, PCDF and Coplanar PCB Congeners in Common Cormorants from the Lake Biwa, Japan.2004

    • Author(s)
      Kubota, A., Iwata, H., Tanabe, S., Yoneda, K., Tobata, S.
    • Journal Title

      Environmental Science and Technology 38

      Pages: 3853-3859

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Identification of CYP1A1 and 1A2 cDNAs, and their mRNA Expressions Related to Levels of Dioxin-like Compounds in Baikal Seal.2004

    • Author(s)
      Hirakawa, S., Iwata, H., Kim, E-Y., Tanabe, S., Miyazaki, N., Petrov, E.A.
    • Journal Title

      Japanese Journal of Environmental Toxicology 7(2)

      Pages: 55-59

    • NAID

      130004542856

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Identification of aryl hydrocarbon receptor 2 in aquatic birds : cDNA clonong of AHR1 and AHR2 and characteristics of their amino acid seaquences2004

    • Author(s)
      Yasui, T.
    • Journal Title

      Marine Environmental Research 58

      Pages: 113-118

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Identification of constitutive androstane receptor cDNAs in northern fur seal (Callorhinus ursinus)2004

    • Author(s)
      Sakai, H.
    • Journal Title

      Marine Environmental Research 58

      Pages: 107-111

    • Related Report
      2004 Annual Research Report
  • [Journal Article] バイカルアザラシCYPIA/1A2c DNAの同定およびダイオキシン類蓄積濃度と各mRNA発現量の関係2004

    • Author(s)
      平川周作
    • Journal Title

      環境毒性学会誌 7(2)

      Pages: 55-59

    • Related Report
      2004 Annual Research Report
  • [Publications] Kim, E-Y.: "Searching for novel CYP members using cDNA library from a minke whale"Marine Environmental Research. 発表予定. (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yasui, T.: "Identification of aryl hydrocarbon receptor 2 in aquatic birds : cDNA clonong of AHR1 and MHR2 and characteristics of their amino acid sequences"Marine Environmental Research. 発表予定. (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sakai, H.: "Cloning and expression of analysis of constitutive androstane receptor cDNAs in Baikal seal (Phoca sibirica) and northern fur seal (Callorhinus ursinus)"Marine Environmental Research. 発表予定. (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] 岩田 久人: "残留性有機汚染物質による水圏野生生物のチトクロムP450発現系への影響"生活衛生. 46・6. 243-249 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Chiba, I.: "Hepatic microsomal cytochrome P45Os and chlorinated hydrocarbons in largha and ribbon seals from Hokkaido, Japan : Differential response of seal species to Ah receptor agonist exposure"Environmental Toxicology and Chemistry. 21・4. 807-815 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Iwata, H.: "Accumulation of coplanar PCB congeners, and induction of cytochrome P450 in seabirds"Proceedings of International Workshop on Marine Pollutlon by Persistent Organic Pollutants. 65-73 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sakamoto, K.: "Accumulation patterns of polychlorinated biphenyl congeners and organochlorine pesticides in Steller's Sea eagles and White-tailed sea eagles, threatened species, in Hokkaido, Japan"Environmental Toxicology and Chemistry. 21・4. 842-847 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Iwata, H.: "Species-specific responses of constitutively active receptor (CAR)-CYP2B coupling : Lack of CYP2B inducer-responsive nuclear translocation of CAR in marine teleost, soup"Comparative Biochemistry and Physiology, Part C. 131. 501-510 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kim, E.Y.: "cDNA cloning of an aryl hydrocarbon receptor from Baikal seals (Phoca sibirica)"Marine Environmental Research. 54・3. 285-290 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 石塚 真由美: "トキシコロギー"朝倉書店. 327 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Chiba, I: "Negative correlation between plasma thyroid hormone levels and chlorinated hydrocarbon levels accumulated in seals from the coast of Hokkaido, Japan"Environmental Toxicology and Chemistry. 20.5. 1092-1097 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Fujita, S: "P450 in wild animals as biomarker of environmental impact"Biomarkers. 6・1. 19-25 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Maruyama, Y: "Inhibitory effects of endogenous dopaminergic neurotoxin, norsalsolinol on dopamine secretion in PC12 rat pheochromocytoma cells"Neurochemistry International. 38・7. 567-572 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Chiba, I: "Hepatic microsomal cyltochrome P450s and chlorinated hydrocarbons in largha and ribbon seals from Hokkaido, Japan : Differential response of seal species to Ah receptor agonist exposure"Environmental Toxicology and Chemistry. 21・4(発表予定). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sakamoto, K: "Accumulation patterns of polychlorinated biphenyl congeners and organochlorine pesticides in Steller's Sea eagles and White-tailed sea eagles, threatened species, in Hokkaido, Japan"Environmental Toxicology and Chemistry. 21・4(発表予定). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Iwata, H: "Species-specific responses of constitutively active receptor (CAR)-CYP2B coupling : Lack of CYP2B inducer-responsive nuclear translocation of CAR in marine teleost, scup"Comparative Biochemistry and Physiology Part C. (発表予定). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kim, E.Y.: "Comparison of dioxin susceptibility between seals inhabiting freshwater and marine environments : Initial characterization of Ah receptors in Baikal seals and Harbor seals"Marine Environmental Research. (発表予定). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] 岩田久人(分担): "海と環境:海が変わると地球が変わる"講談社. 244 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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