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Mechanisms of Reproductive Toxicity by Endocrine Disrupting Chemicals

Research Project

Project/Area Number 11307007
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Public health/Health science
Research InstitutionKansai Medical University

Principal Investigator

TOKUNAGA Rikio  Kansai Medical University Faculty of Medicine Professor, 医学部, 教授 (40121959)

Co-Investigator(Kenkyū-buntansha) ENDO Yoko (ICHIKAWA Yoko)  Kansai Medical University Faculty of Medicine Assistant Professor, 医学部, 講師 (50193438)
KOHNO Hirao  Kansai Medical University Faculty of Medicine Assistant Professor, 医学部, 講師 (30148522)
古川 高子  関西医科大学, 医学部, 講師 (00221557)
Project Period (FY) 1999 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥28,390,000 (Direct Cost: ¥25,900,000、Indirect Cost: ¥2,490,000)
Fiscal Year 2002: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2001: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
Fiscal Year 2000: ¥6,400,000 (Direct Cost: ¥6,400,000)
Fiscal Year 1999: ¥11,200,000 (Direct Cost: ¥11,200,000)
KeywordsEndocrine Disrupting Chemicals / Reproductive Toxicity / Estrogen / 内分泌撹乱物質
Research Abstract

To evaluate the effects of endocrine disrupting chemicals on reproductive functions in human beings, we focused on phytoestrogens that are taken up through food intake. We tested the estrogenic and antiestrogenic effects of two phytoestrotens, resveratrol and naringenin. Resveratrol is reported to act as a "super agonist" in human MCF-7 cells, which was confirmed in the present study. However, in HeLa cells or COS-7 cells, the maximal activation by resveratrol was lower than that by estradiol. In yeast, the resveratrol concentration required for the maximal activation was 50-fold higher than in MCF-7 cells, while there was no difference in optimal estradiol concentrations. Difference in optimal concentration for the maximal activation was observed also observed for naringenin. Whether resveratrol acts as an antagonist was investigated. No antagonistic activity was detected with resveratrol in all reporter assay systems we used. Resveratrol and estradiol exhibited an additive effect in COS-7 or yeast cells, whereas synergistic effect was observed in 293 cells. In contrast to the complex interactions between resveratrol and estradiol, naringenin and estradiol exhibited additive effect in all reporter assay systems we used including yeast. Our study indicates that estrogenic and antiestrogenic activity of structurally diverse phytoestrogens is complex and unpredictable. To screen the estrogenic ingredients, possibly found in beverages, we prepared the extracts from beer hops and herb tea mixtures and determined their estrogenic activities. Two hops and four herb tea mixtures gave positive results. The common ingredients contained only in those herb tea mixtures was liquorice root.

Report

(5 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] Taketani S: "Structure and transcriptional regulation of the mouse ferrochelatase gene"Gene. 227. 117-124 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Masuya Y: "MAP kinase-independent induction of proto-oncogene c-fos mRNA by hemin in human cells"Biochem Biophs Res Commun. 260. 289-295 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mohri T: "Activated Rac1 selectively up-regulates the expression of integrin a6b4 and induces cell adhesion and membrane ruffles of nonadherent colon cancer Colo201 cells"Exp Cell Res. 253. 533-540 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Oyaizu Y: "A crucial role of caspase 3 and caspase 8 in paclitaxel-induced apotosis"Mol Cell Biol Res Commun. 2. 36-41 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Adachi Y: "Apotosis of colorectal adenocarcinoma induced by 5-FU and/or IFN-gamma through caspase 3 and caspase 8"Int J Oncol. 15. 1191-1196 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ishihara R: "ELISA for rinary trehalase with monoclonal antibodies : a technique for assessment of renal tubular damage"Clin Chem. 46. 636-643 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ikebukuro K: "Morphological change, loss of deltapsi(m) and activation of caspases upon apoptosis of colorectal adenocarcinoma induced by 5-FU"Cancer Lett. 153. 101-108 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 河野比良夫: "内分泌撹乱化学物質(環境ホルモン)問題について"生物試料分析. 23. 385-392 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Furukawa T: "Involvement of PLAGL2 in activation of iron deficient-and hypoxia-induced gene expression in mouse cell lines"Oncogene. 20. 4718-4727 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Taketani S: "Structure and transcriptional regulation of the mouse ferrochelatase gene"Gene. 227. 117-124 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Masuya Y: "MAP kinase-independent induction of proto-oncogene c-fos mRNA by hemin in human cells"Biochem Biophs Res Commun. 260. 289-295 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mohri T: "Activated Rac1 selectively up-regulates the expression of integrin a6b4 and induces cell adhesion and membrane ruffles of nonadherent colon cancer Colo201 cells"Exp Cell Res. 253. 533-540 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Oyaizu Y: "A crucial role of caspase 3 and caspase 8 in paclitaxel-induced apoptosis"Mol Cell Biol Res Commun. 2. 36-41 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Adachi Y: "Apoptosis of colorectal adenocarcinoma induced by 5-FU and/or IFN-gamma through caspase 3 and caspase 8"Int J Oncol. 15. 1191-1196 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ishihara R: "ELISA for rinary trehalase with monoclonal antibodies: a technique for assessment of renal tubular damage"Clin Chem. 46. 636-643 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tanabe A: "Analysis of the candidate genes responsible for non-syndromic cleft lip and palate in Japanese people"Clin Sci. 99. 105-111 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ikebukuro K: "Morphological change, loss of deltapsi(m) and activation of caspases upon apoptosis of colorectal adenocarcinoma induced by 5-FU"Cancer Lett. 153. 101-108 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Furukawa T: "Involvement of PLAGL2 in activation of iron deficient- and hypoxia-induced gene expression in mouse cell lines"Oncogene. 20. 4718-4727 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] T.Fukukawa: "Involvement of PLAGL2 in activation of iron-deficient-and hopoxia -induced gene expression in mouse cells"Oncogene. 20・34. 4718-4727 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] A.Mizutani: "A Zinc-finger protein, PLAGL2, indeces the expression of a proapoptic protein Nip3, leading to cellular apoptosis"J. Biol. Chem.. (in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] 河野比良夫: "内分泌撹乱化学物質(環境ホルモン)問題について"生物試料分析. 23・5. 385-392 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] T.Furukawa: "Assembly of partial TFIID complexes in mammalian cells reveals distinct activities associated with individual TATA box-binding protein-associated factors"J.Biol.Chem.. 275・38. 29847-29856 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] A.Tanabe: "Analysis of the candidate genes responsible for non-syndromic cleft lip and palate in Japanese people"Clin.Sci.. 99・2. 105-111 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] R.Ishihara: "ELISA for urinary trehalase with monoclonal antibodies : a techinique for assessment of renal tubular damage"Clin.Chem.. 46・5. 636-643 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] K.Ikebukuro: "Morphological change, loss of deltapsi (m) and activation of caspases upon apotosis of colorectal adenocarcinoma induced by 5-FU"Cancer Lett.. 153・1〜2. 101-108 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] S.Taketani: "Structure and transcriptional regulation of the mouse ferrochelatase gene"Gene. 227・2. 117-124 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Y.Masuya: "MAP kinase-independent induction of proto-oncogene c-fos mRNA by hemin in human cells"Biochem. Biophys, Res. Commun.. 260・1. 289-295 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Y.Adachi: "Apoptosis of colorectal adenocarcinoma induced by 5-FU and/or IFN-γ through caspase 3 and caspase 8"Int.J.Oncol.. 15・6. 1191-1196 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] T.Mohri: "Actirated Rac 1 selectively up-regulates the expression of integrin α6β4 and induces cell adhesion and membrane ruffles of nonadherent colon cancer Colo 201 cells"Exp.Cell Res.. 253・2. 533-540 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] R.Ishihara: "ELISA for urinary trehalase using monoclonal antibodies: A technique for assessment of renal tubular damage"Clin.Chem.. (in press).

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2021-11-22  

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