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Metabolism and endocrine disrupting action of environmental pollutants

Research Project

Project/Area Number 11557199
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section展開研究
Research Field Environmental pharmacy
Research InstitutionHiroshima University School of Medicine

Principal Investigator

KITAMURA Shigeyuki  Hiroshima University School of Medicine, Associate Professor, 医学部, 助教授 (40136057)

Co-Investigator(Kenkyū-buntansha) OHTA Shigeru  Hiroshima Univ.Sch.Med.Professor, 医学部, 教授 (60160503)
WATANABE Hiromitu  Dept.Cancer Res.Hiroshima Univ.Professor, 原爆放射能医学研究所, 教授 (00034653)
ARIZONO Koji  Faculty of Environmental and Symbiotic Sciences Prefectural University of Kumamoto, Professor, 環境共生学部, 教授 (70128148)
SUGIHARA Kazumi  Hiroshima Univ.Sch.Med.Research Associate, 医学部, 教務員 (20271067)
YOSHIHARA Shin'ichi  Hiroshima Univ.Sch.Med.Assoc.Prof., 医学部, 助教授 (00037607)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥12,300,000 (Direct Cost: ¥12,300,000)
Fiscal Year 2000: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1999: ¥10,200,000 (Direct Cost: ¥10,200,000)
Keywordsendocrine disruptor / proestrogen / estrogen / metabolic activation / vitellogenin / trans-stilbene / biphenyl / drug metabolizing enzyme / トランス-スチルベン / トランスースチルベンオキシド
Research Abstract

The effect of the metabolism of endocrine disruptors on the estrogenic activity was examined in this study.
1. The estrogenic activity was estimated by the reporter assay using human breast cancer cell line MCF-7 and growth assay using rat pituitary tumor cell line MtT/E-2. When bisphenol A and nonylphenol were incubated with rat liver microsomes in the presence of NADPH, the estrogenic activities of these compounds were decreased. On the contrary, biochanin A and methoxychlor were activated by the incubation with liver microsomes. In contrast, the estrogenic activities of p, p'-DDT and o, p'-DDT were not effected by the liver microsomal metabolism. 2. We found some proestrogens which were not estrogenic and produced their activities after the metabolism. As proestrogens, we detected trans-stilbene, biphenyl, diphenylmethane, dibenzyl, 2, 2-diphenylpropane, benzylideneacetone, styrene, diphenylamine, diphenylsulfone, pyrene and chalchone by screening the estrogenic activities of their metabolites. 3. These proestrogens were converted to their hydroxylated active metabolites in vivo and in vitro in rats. The hydroxylation was mediated by liver microsomal cytochrome P450 2B1 or 1A1. 4. trans-Stilbene did not exhibit reproductive toxicity in mice. However, the active metabolite, trans-4,4'-dihydroxystilbene, induced the testicular toxicity in mice. 5. When male goldfish were kept in the water containing trans-stilbene(5×10^<-6> M)for five days, the vitellogenin level in blood was markedly increased. trans-4-Hydroxystilbene and trans-4,4'-dihydroxystilbene were detected as in vivo metabolites in the tank water kept the fish. trans-Stilbene was also converted to these hydroxylated metabolites by liver microsomes of the fish. This fact suggests that trans-stilbene was transformed to the active metabolites in the fish. 6. p, p'-DDT and o, p'-DDT, and their related compounds showed the neurotoxicity on rat cerebellum cells in the range of 1×10^<-8>-10^<-7>M.

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (62 results)

All Other

All Publications (62 results)

  • [Publications] Shigeyuki Kitamura: "Reductive dechlorination of p, p'-DDT mediated by hemoproteins in hepatopancreas and blood of goldfish, Carassius auratus."Journal of Health Science. 45(4). 217-221 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shigeyuki Kitamura: "Reductive metabolism in vivo of trans-4-phenyl-3-buten-2-one in rats and dogs."Drug Metabolism and Disposition. 27(7). 767-769 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kazumi Sugihara: "Ah-receptor mediated induction of liver xanthine oxidase/xanthine dehydrogenase by 2, 3, 7, 8-TCDD"Organohalogen compounds. 42. 425-428 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shigeyuki Kitamura: "Conversion of dieldrin to aldrin by intestinal bacteria in rats"Biological and Pharmaceutical Bulletin. 22(8). 880-882 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shigeyuki Kitamura: "Interconversion between fenthion and fenthion sulfoxide in goldfish, Carassius auratus."Journal of Health Science. 45(5). 266-270 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shigeyuki Kitamura: "Effect of fenthion on the level of vitellogenin in goldfish, Carassius auratus."Journal of Health Science. 45(5). 262-265 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shigeyuki Kitamura: "Pseudoenzymatic Reduction of N-Hydroxy-2-acetylaminofluorene to 2-Acetylaminofluorene Mediated by Cytochrome P450"Carcinogenesis. 20(2). 347-350 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yuji Okamoto: "Microsomal Carbonyl Reductase Responsible for Reduction of 4-Phenyl-3-buten-2-one in Rats."IUBMB Life. 48(5). 543-547 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shigeyuki Kitamura: "Whole-body Metabolism of the Organophosphorus Pesticide, Fenthion, in Goldfish, Carassius Auratus."Comparative Biochemistry and Physiology. 126. 259-266 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shigeyuki Kitamura: "Nonenzymatic Reduction of N-Hydroxy-2-acetylaminofluorene to 2-Acetylaminofluorene by Heme in the Presence of Hydroquinones"Journal of Health Science. 4(1). 66-69 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kazumi Sugihara: "Reduction of Hydroxamic Acids to the Corresponding Amides Catalyzed by Rabbit Blood."Xenobiotica. 30(5). 457-467 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shigeyuki Kitamura: "Reduction of Stilbene Oxide and Styrene Oxide to the Corresponding Alkenes by Intestinal Bacteria."Xenobiotica. 30(4). 359-369 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shigeyuki Kitamura: "Reductive Metabolism of Stilbene Oxide and Styrene Oxide to the Olefins in Rats"Biological and Pharmaceutical Bulletin. 23(2). 265-268 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kazumi Sugihara: "Induction of Liver Xanthine Dehydrogenase/Xanthine Oxidase by 2, 3, 7, 8-TCDD and Cobalt Chloride."Organohalogen Compounds. 49. 247-250 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kazumi Sugihara: "Metabolic Activation of the Proestrogens trans-Stilbene and trans-Stilbene Oxide by Rat Liver Microsomes."Toxicology and Applied Pharmacology. 167. 46-54 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Osamu Ueda: "Metabolism of 2-Nitrofluorene, an Environmental Pollutant, and 2-Acetylaminofluorene in Fish."Bull.Environ.Contam.Toxicol.. 66(3). 371-378 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Osamu Ueda: "Metabolism of 2-Nitrofluorene, 2-Aminofluorene and 2-Acetylaminofluorene in Rat and Dog and the Role of Intestinal Bacteria."Xenobiotica. (in press). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kazumi Sugihara: "Aryl Hydrocarbon Receptor-Mediated Induction of Xanthine Oxidase/Xanthine Dehydrogenase Activity by TCDD."Biochemical and Biophysical Research Communications. (in press). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 北村繁幸: "新しい臨床検査:内分泌撹乱物質の検査"株式会社 現代医療社(印刷中). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shigeyuki Kitamura: "Reductive dechlorination of p, p'-DDT Mediated by Hemoproteins in Hepatopancreas and Blood of Goldfish, Carassius auratus."Journal of Health Science. 45(4). 217-221 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shigeyuki Kitamura: "Reductive Metabolism in vivo of trans-4-Phenyl-3-buten-2-one in Rats and Dogs."Drug Metabolism and Disposition. 27(7). 767-769 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kazumi Sugihara: "Ah-receptor Mediated Induction of Liver Xanthine Oxidase/Xanthine Dehydrogenase by 2, 3, 7, 8-TCDD."Organohalogen Compounds. 42. 425-428 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shigeyuki Kitamura: "Conversion of Dieldrin to Aldrin by Intestinal Bacteria in Rats."Biological and Pharmaceutical Bulletin. 22(8). 880-882 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shigeyuki Kitamura: "Interconversion between Fenthion and Fenthion Sulfoxide in Goldfish, Carassius Auratus."Journal of Health Science. 45(5). 266-270 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shigeyuki Kitamura: "Effect of Fention on the Level of Vitellogenin in Goldfish, Carassius Auratus."Journal of Health Science. 45(5). 262-265 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shigeyuki Kitamura: "Pseudoenzymatic Reduction of N-Hydroxy-2-acetylaminofluorene to 2-Acetylaminofluorene Mediated by Cytochrome P450."Carcinogenesis. 20(2). 347-350 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yuji Okamoto: "Microsomal Carbonyl Reductase Responsible for Reduction of 4-Phenyl-3-buten-2-one in Rats."IUBMB Life. 48(5). 543-547 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shigeyuki Kitamura: "Whole-body Metabolism of the Organophosphorus Pesticide, Fenthion, in Goldfish, Carassius Auratus."Comparative Biochemistry and Physiology. 126. 259-266 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shigeyuki Kitamura: "Nonenzymatic Reduction of N-Hydroxy-2-acetyl-aminofluorene to 2-Acetylaminofluorene by Heme in the Presence of Hydropuinones."Journal of Health Science. 46(1). 66-69 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kazumi Sugihara: "Reduction of Hydroxamic Acids to the Corres-ponding Amides Catalyzed by Rabbit Blood."Xenobiotica. 30(5). 457-46 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shigeyuki Kitamura: "Reduction of Stilbene Oxide and Styrene Oxide to the Corresponding Alkenes by Intestinal Bacteria."Xenobiotica. 30(4). 359-369 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shigeyuki Kitamura: "Reductive Metablism of Stilbene Oxide and Styrene Oxide to the Olefins in Rats"Biological and Pharmaceutical Bulletin. 23(2). 265-268 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kazumi Sugihara: "Induction of Liver Xanthine Dehydrogenase/Xanthine Oxidase by 2, 3, 7, 8-TCDD and Cobalt Chloride."Organohalogen Compounds. 49. 247-250 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kazumi Sugihara: "Metabolic Activation of the Proestrogens trans-Stilbene and trans-Stilbene Oxide by Rat Liver Microsomes."Toxicology and Applied Pharmacology. 167. 46-54 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Osamu Ueda: "Metabolism of 2-Nitrofluorene, an Environmental Pollutant, and 2-Acetylaminofluorene in Fish."Bull.Environ.Contam.Toxical.. 66(3). 371-378 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Osamu Ueda: "Metabolism of 2-Nitrofluorene, 2-Aminofluorene and 2-Acetylaminofluorene in Rat and Dog and the Role of Intestinal Bacteria."Xenobiotica. (in press). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kazumni Sugihara: "Aryl Hydrocarbon Receptor-Mediated Induction of Xanthine Oxidase/Xanthine Dehydrogenase Activity by TCDD."Biochemical and Biophysical Research Communications. (in press). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shigeyuki Kitamura: "Reductive dechlorination of p,p'-DDT mediated by hemoproteins in hepatopancreas and blood of goldfish, Carassius auratus."Journal of Health Science. 45(4). 217-221 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Shigeyuki Kitamura: "Reductive metabolism in vivo of trans-4-phenyl-3-buten-2-one in rats and dogs."Drug Metabolism and Disposition. 27(7). 767-769 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kazumi Sugihara: "Ah-receptor mediated induction of liver xanthine oxidase/xanthine dehydrogenase by 2,3,7,8-TCDD"Organohalogen compounds. 42. 425-428 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Shigeyuki Kitamura: "Conversion of dieldrin to aldrin by intestinal bacteria in rats"Biological and Pharmaceutical Bulletin. 22(8). 880-882 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Shigeyuki Kitamura: "Interconversion between fenthion and fenthion sulfoxide in goldfish, Carassius auratus."Journal of Health Science. 45(5). 266-270 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Shigeyuki Kitamura: "Effect of fenthion on the level of vitellogenin in goldfish, Carassius auratus."Journal of Health Science. 45(5). 262-265 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Shigeyuki Kitamura: "Pseudoenzymatic Reduction of N-Hydroxy-2-acetylaminofluorene to 2-Acetylaminofluorene Mediated by Cytochrome P450"Carcinogenesis. 20(2). 347-350 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yuji Okamoto: "Microsomal Carbonyl Reductase Responsible for Reduction of 4-Phenyl-3-buten-2-one in Rats."IUBMB Life. 48(5). 543-547 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Shigeyuki Kitamura: "Whole-body Metabolism of the Organophosphorus Pesticide, Fenthion, in Goldfish, Carassius Auratus."Comparative Biochemistry and Physiology. 126. 259-266 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Shigeyuki Kitamura: "Nonenzymatic Reduction of N-Hydroxy-2-acetylaminofluorene to 2-Acetylaminofluorene by Heme in the Presence of Hydroquinones"Journal of Health Science. 46(1). 66-69 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kazumi Sugihara: "Reduction of Hydroxamic Acids to the Corresponding Amides Catalyzed by Rabbit Blood."Xenobiotica. 30(5). 457-467 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Shigeyuki Kitamura: "Reduction of Stilbene Oxide and Styrene Oxide to the Corresponding Alkenes by Intestinal Bacteria."Xenobiotica. 30(4). 359-369 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Shigeyuki Kitamura: "Reductive Metabolism of Stilbene Oxide and Styrene Oxide to the Olefins in Rats"Biological and Pharmaceutical Bulletin. 23(2). 265-268 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kazumi Sugihara: "Induction of Liver Xanthine Dehydrogenase/Xanthine Oxidase by 2,3,7,8-TCDD and Cobalt Chloride."Organohalogen Compounds. 49. 247-250 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kazumi Sugihara: "Metabolic Activation of the Proestrogens trans-Stilbene and trans-Stilbene Oxide by Rat Liver Microsomes."Toxicology and Applied Pharmacology. 167. 46-54 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Osamu Ueda: "Metabolism of 2-Nitrofluorene, an Environmental Pollutant, and 2-Acetylaminofluorene in Fish."Bull.Environ.Contam.Toxicol.. 66(3). 371-378 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Osamu Ueda: "Metabolism of 2-Nitrofluorene, 2-Aminofluorene and 2-Acetylaminofluorene in Rat and Dog and the Role of Intestinal Bacteria."Xenobiotica. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kazumi Sugihara: "Aryl Hydrocarbon Receptor-Mediated Induction of Xanthine Oxidase/Xanthine Dehydrogenase Activity by TCDD."Biochemical and Biophysical Research Communications. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] 北村繁幸: "新しい臨床検査:内分泌撹乱物質の検査"株式会社 現代医療社(印刷中). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Shigeyuki Kitamura: "Reductive dechlorination of p,p'-DDT mediated by hemoproteins in hepatopancreas and blood of goldfish, Carassius auratus."Journal of Health Science. 45(4). 217-221 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Shigeyuki Kitamura: "Reductive metabolism in vivo of trans-4-pheny1-3-buten-2-one in rats and dogs."Drug Metabolism and Disposition. 27(7). 767-769 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kazumi Sugihara: "Ah-receptor mediated induction of liver xanthine oxidase/xanthine dehydrogenase by 2,3,7,8-TCDD"Organohalogen compounds. 42. 425-428 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Shigeyuki Kitamura: "Conversion of dieldrin to aldrin by intestinal bacteria in rats"Biological and Pharmaceutical Bulletin. 22(8). 880-882 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Shigeyuki Kitamura: "Interconversion between fenthion and fenthion sulfoxide in goldfish, Carassius auratus."Journal of Health Science. 45(5). 266-270 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Shigeyuki Kitamura: "Effect of fenthion on the level of vitellogenin in goldfish, Carassius auratus."Journal of Health Science. 45(5). 262-265 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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