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Formation of Hydroxylated Metabolites Responsible for the Toxicity of Brominated Flame Retardants and Thyroid Hormone Disrupting Action

Research Project

Project/Area Number 18590118
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Environmental pharmacy
Research InstitutionNihon Pharmaceutical University

Principal Investigator

KITAMURA Shigeyuki  Nihon Pharmaceutical University, School of Pharmacy, Professor (40136057)

Co-Investigator(Kenkyū-buntansha) FUJIMOTO Nariaki  Hiroshima University, Reseanch Institute for Radiation Biology and Medicine, Associate Professor (40243612)
KASHIWAGI Akihiko  Hiroshima University, Graduate School of Sciences, Professor (50106796)
OHTA Shigeru  Hiroshima University, Graduate Shool of Biomedical Scienoes, Professor (60160503)
SUGIHARA Kazumi  Hiroshima University, Graduate Shool of Biomedical Sciences, Research Associate (20271067)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,680,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥180,000)
Fiscal Year 2007: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2006: ¥2,900,000 (Direct Cost: ¥2,900,000)
KeywordsEndocrine disruptor / Brominated flame retardant / Tetrabromobisphenol A / Polybromodiphenyl ether / Thyroid hormonal activity / Estrogenic activity / Metabolic activation / Amphibian metamorphosis / ブロム化難燃剤 / ポリブロモジフェニールエーテル / 甲状腺ホルモン / 内分泌撹乱作用
Research Abstract

Endocrine-disrupting activity of some brominated flame retardants was examined. 1) The thyroid hormone-disrupting activity of tetrabromobisphenol A, tetrachlorobisphenol A, some 4-hydroxylated polybromodiphenyl ethers was observed in the assay of binding to thyroid hormone receptor. These chemicals also showed thyroid hormonal effect on GH3 cell. However, polybrominated diphenyl ethers and bisphenol A did not exhibit the activity. Especially, tetrabromobisphenol A exhibited the highest thyroid hormonal activity. 3, 5-Substituted bromide is an essential factor for the thyroid hormonal activity. 2) 4-Hydroxy-2, 2', 4-tribromodiphenyl ether exhibited estrogenic activity in the reporter assay using human breast cancer cell line MCF-7. In this case, 3, 5-dibromo substitution decreased the estrogenic activity. 3) The action of these chemicals was also estimated by amphibian metamorphosis using tadpole. The tail of tadopole was shortened by the addition of triiodothyronine (T3). These chemicals showed antagonistic effect against the T3-induced tadpole tail regression. These facts suggest that hydroxylated brominated flame retardants exhibited endocrine-disrupting effect in the worldwide life.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (28 results)

All 2007 2006

All Journal Article (18 results) (of which Peer Reviewed: 3 results) Presentation (9 results) Book (1 results)

  • [Journal Article] Comparative study of aryl hydrocarbon receptor ligand activities of six chemicals in vitro and in vivo2007

    • Author(s)
      Sugihara, et. al.
    • Journal Title

      Archives of Toxicology 82

      Pages: 5-11

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Effects of environmental antiandrogenic chemicals on expression of androgen-responsive genes in rat prostate lobes2007

    • Author(s)
      Suzuki, et. al.
    • Journal Title

      Journal of Health Sciences 53

      Pages: 401-405

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] The in vitro metabolism of a pyrethroid insecticide,permethrin,and its hydrolyzed products in rats2007

    • Author(s)
      Nakamura, et. al.
    • Journal Title

      Toxicology 235

      Pages: 176-184

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] In vivo function of the 5'fianking region of mouse estrogen receptor beta gene. Yoshito Tezuka, Kyoko Takahashi, Tomoharu Suzuki, Shigeyuki Kitamura2007

    • Author(s)
      N., Fujimoto, O., Nakajima, S., Kitamura, S., Ohta
    • Journal Title

      J Steroid Biochem Mol Biol 105

      Pages: 57-62

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Novel metabolic pathways ofp-n-nonylphenol catalyzed by cytochrome P450 and estrogen recentor bindina activity of new metabolites2007

    • Author(s)
      Shigeru, Ohta, Shigeo, Nakamura, Tadahiko, Mashino
    • Journal Title

      Journal of Health Science 53(5)

      Pages: 552-561

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Effects of environmental antiandrogenic chemicals on expression of androgen -responsive genes in rat prostate lobes2007

    • Author(s)
      T., Suzuki, N., Fujimoto, S., Kitamura, S., Ohta
    • Journal Title

      Journal of Health Science 53(4)

      Pages: 401-405

    • NAID

      110006366919

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] The in vitro metabolism of a pyrethroid insecticide, permethrin, and its hydrolyzed oroducts in rats2007

    • Author(s)
      Y., Nakamura, K., Sugihara, T., Sone, M., Isobe, S., Ohta, S., Kitamura
    • Journal Title

      Toxicology 235

      Pages: 176-184

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Quantitative determination of lobe specificity of mRNA expression of androgen -dependent genes in the rat prostate gland2007

    • Author(s)
      T., Suzuki, N., Fujimoto, S., Kitamura, S., Ohta
    • Journal Title

      Endocrine Journal 54(1)

      Pages: 123-132

    • NAID

      10019479578

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Comparative study of aryl hydrocarbon receptor ligand activities of six chemicals in vitro and in vivo2007

    • Author(s)
      K., Sugihara, T., Okayama, S., Kitamura, K., Yamashita, M., Yasuda, S., Miyairi, Y., Minobe, S., Ohta
    • Journal Title

      Archives of Toxicology 82

      Pages: 5-11

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Quantitative determination of lobe specificity of mRNA expression of androgen-dependent genes in the rat prostate gland2007

    • Author(s)
      Suzuki et al.
    • Journal Title

      Endocrine Journal 54(1)

      Pages: 123-132

    • Related Report
      2006 Annual Research Report
  • [Journal Article] The in vitro metabolism of a pyrethroid insecticide, permethrin, and its hydrolyzed products in tars. Toxicology2007

    • Author(s)
      Nakamura et al.
    • Journal Title

      Toxicology (In press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Comparative study of aryl hydrocarbon receptor ligand activities of six chemicals in vitro and in vivo2007

    • Author(s)
      Sugihara et al.
    • Journal Title

      archives of Toxicology (In press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Suppression of amphibian metamorphosis by bisphenol A and related chemical substances2006

    • Author(s)
      Y., Goto, S., Kitamura, K., Kashiwagi, K., Oofusa, O., Tooi, K., Yoshizato, J., Sato, S., Ohta, A., Kashiwagi
    • Journal Title

      Journal of Health Sciences 52(2)

      Pages: 160-168

    • NAID

      110006163232

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Effects of stilbene and related compounds on reproductive organs in B6C3F1/Crj mouse H. Fujita, Y. Okimura, T. Utsumi, S. Kitamura, H. Kuroki, T. Otsuki, J. Sasaki, A. Kashiwag2006

    • Author(s)
      S., Sanoh, S., Kitamura, R., Kohta, K., Sugihara, S., Ohta, H., Watanabe
    • Journal Title

      Journal of Health Sciences 52(5)

      Pages: 613-622

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] 4-Hydroxy-3, 5, 3', 4'-tetrachlorobiphenyl induced membrane permeability transition in isolated rat liver mitochondria2006

    • Author(s)
      K., Utsumi
    • Journal Title

      J. Clin. Biochem. Nutr. 38

      Pages: 167-175

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Suppression of amphibian metamorphosis by bisphenol A and related chemical substances.2006

    • Author(s)
      Goto et al.
    • Journal Title

      Journal of Health Sciences 52(2)

      Pages: 160-168

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 4-Hydroxy-3,5,3',4'-tetrachlorobiphenyl induced membrane permeability transition in isolated rat liver mitochondria2006

    • Author(s)
      fujita et al.
    • Journal Title

      J. Clin. Biochem. Nutr. 38

      Pages: 167-175

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Effects of stilbene and related compounds on reproductive organs in B6C3F1/Crj mouse2006

    • Author(s)
      Sanoh et al.
    • Journal Title

      Journal of Health Sciences 52(5)

      Pages: 613-622

    • Related Report
      2006 Annual Research Report
  • [Presentation] Thyroid hormonal and estrogenic activity of OH-PCB and OH-PBDE in cell culture2007

    • Author(s)
      Kitamura, et. al.
    • Organizer
      DIOXIN 2007
    • Place of Presentation
      Tokyo
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] Thyroid hormonal and estrogenic activity of OH-PCB and OH-PBDE in cell culture2007

    • Author(s)
      S., Kitamura, T., Suzuki, K., Sugihara, N., Uramaru, H., Kuroki, N., Fujimoto, S., Ohta
    • Organizer
      DIOXIN 2007
    • Place of Presentation
      Tokyo Japan
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] The S-oxidation of PCB methyl ulfoxise to PCB methyl sulfone with animal liver microsomes and human cytochrome P4502007

    • Author(s)
      H., Kuroki, H., Nakai, A., Toda, M., Mitsutake, R., Eyanagi, S., Kitamura
    • Organizer
      DIOXIN 2007
    • Place of Presentation
      Tokyo Japan
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Screening of AhR-binding, estrogenic and antiandrogenic activities of benzophenone derivatives used as UV stabilizers and sunscreens2007

    • Author(s)
      K., sugihara, S., Shinohara, T., Suzuki, N., Fujimoto, S., Kitamura, S., Ohta
    • Organizer
      DIOXIN 2007
    • Place of Presentation
      Tokyo Japan
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Parabens and phthalates : Their metabolism, AhR ligand activity, estrogenic Activity, and P450-inhibitory activity2007

    • Author(s)
      H., Oz-aki, S., Shinohara, S., Tange, K., Sugihara, S., Kitamura, S., Ohta
    • Organizer
      DIOXIN 2007
    • Place of Presentation
      Tokyo Japan
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Metabolism of carbamate pesticides by liver microsomes and plasma of human and rat2007

    • Author(s)
      S., Tange, S., Kitamura, K., Sugihara, S., Ohta
    • Organizer
      8th International ISSX Meeting
    • Place of Presentation
      Sendai Japan
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Developmental changes of aldehyde oxidase activity in liver cytosol of young ehildren2007

    • Author(s)
      Y., Tayama, K., Sugihara, S., Kitamura, S., Ohta
    • Organizer
      8th International ISSX Meeting
    • Place of Presentation
      Sendai Japan
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] In vivo and in vitro metabolism of zaleplon in chimeric mice with humanized liver2007

    • Author(s)
      C., Tanoue, K., Sugihara, S., Kitamura, T., Inoue, T., Horie, S., Ohta
    • Organizer
      8th, International ISSX Meeting
    • Place of Presentation
      Sendai Japan
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Chimeric mice with humanized liver as a model to predict diazepam metabolism in humans.2007

    • Author(s)
      T., Inoue, K., Sugihara, S., Kitamura, H., Ohshita, T., Horie, S., Ohta
    • Organizer
      8th International ISSX Meeting
    • Place of Presentation
      Sendai Japan
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] Toxicology of Organophosphate and Carbamate Compounds (Endocrine disruption by organophosphate and carbamate pesticides)2006

    • Author(s)
      Kitamura et al.分担(R.C.Gupta編集)
    • Total Pages
      763
    • Publisher
      Elsevier
    • Related Report
      2006 Annual Research Report

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Published: 2006-04-01   Modified: 2016-04-21  

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