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Biochemical and molecular mechanisms of beneficial effects for human health by phytoestrogens

Research Project

Project/Area Number 11672235
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Environmental pharmacy
Research InstitutionNational Institute of Health Sciences

Principal Investigator

OZAWA Shogo  National Institute of Health Sciences, Section chief, 薬理部, 室長 (20185581)

Project Period (FY) 1999 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2001: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2000: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1999: ¥2,000,000 (Direct Cost: ¥2,000,000)
KeywordsEstrogenicity / Human / Drug Metabolizing enzymes / Sulfotransferase / detoxification / gene expression / estrogen responsiveness / phytoestrogens / 代謝活性化
Research Abstract

In this study, estrogenicity of bisphenol A and phytoestrogens such as genistein was compared in human breast cancer MCF-7 cells using so called E-screen assay. We also established induction of expression of pS2 gene, an estrogen-resposive gene, after exposure of MCF-7 cells to chemicals with estrogenicity. Estrogenic activities of daidzein, naringenin, kaempfenol were weaker than that of genistein. For detoxification pathway of estrogenic compounds, sulfoconjugation of bisphenol A and phytoestrogens was catalyzed by human hepatic microsomes. On the basis of Km values, affinity of bisphenol A to sulfotransferase seemed to be higher than that of phytoestrogens. A form of thermostable phenol-sulfating sulfotransferase, ST1A3, was identified as a bisphenol A-sulfating sulfotransferase.
Difference in the mechanisms of estrogenicity between phytoestrogens and bisphenol A was not, however, achieved. It would be possible by analyses of gene expression after exposure of MCF-7 cells to phytoestrogens, and bisphenol A whose toxic action is suspected due to its estrogenic action.

Report

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

    (29 results)

All Other

All Publications (29 results)

  • [Publications] 小澤 正吾: "Sulfating activity and stability of cDNA expressed allozymes of human phenol sulfotransferase, STIA311 and STIA312, both of which ganister"J. Biochem. (Tokyo). 126. 271-277 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 小澤 正吾: "ヒト肝薬物代謝活性形質診断法の最近までの進歩"国立医薬品食品衛生研究所報告. 117. 63-79 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Frame, L.T., 小澤 正吾: "A simple colorimetric assay for phenotyping the major human thermastable phend sulfotransferase (SULT1A1) using platelet cytosds"Drug Metabol. Dispos.. 28. 1063-1968 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nowell, S., 小澤正吾: "Relationship of phenol sulfotransferase activity (SULT1A1) genotype to sulfotransferase phenotype in platelet cytozol"Pharmacogenetics. 10. 789-797 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 小澤正吾: "ヒト組織フェノール硫酸転移酵素の遺伝的多型性"薬物動態. 15. 171-176 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 小澤正吾: "薬物代謝酵素の遺伝子多型と疾病感受性・薬物反応性の個体差"Molecular Medicine. 38. 1146-1150 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] S. Ozawa, M. Shimizu, T. Katoh, A. Miyajima, Y. Ohno, Y. Matsumoto, M. Fukuoka, Y.-M. Tang, N.P. Lang and F.F. Kadlubar: "Sulfating-activity and stability of cDNA-expressed allozymes of human phenol sulfotransferase, ST1A3*1 ((213)Arg) and ST1A3*2 ((213)His), both of which exist in Japanese as well as Caucasians"J Biochem (Tokyo). 126(2). 271-277 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] S. Ozawa: "Diagnosis of hepatic enzyme activities of drug metabolizing enzymes-phenoyping and genotyping"Bull Natl. Inst. Health Sci. 117. 63-79 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] L. T. Frame, S. Ozawa, S. A. Nowell, H. C. Chou, R. R. DeLongchamp, D. R. Doerge, N. P. Lang and F. F. Kadlubar: "A simple colorimetric assay for phenotyping the major human thermostable phenol sulfotransferase (SULT1A1) using platelet cytosols"Drug Metab Dispos. 28(9). 1063-1068 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] S. Nowell, C. B. Ambrosone, S. Ozawa, S. L. MacLeod, G. Mrackova, S. Williams, J. Plaxco, F. F. Kadlubar and N. P. Lang: "Relationship of phenol sulfotransferase activity (SULT1A1) genotype to sulfotransferase phenotype in platelet cytosol"Pharmacogenetics. 10(9). 789-797 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] S. Ozawa, M. Shimizu, Y. Matsumoto, M. Fukuoka, T. Katoh, Y. Ohno: "Genetic polymorphisms of human tissue phenol sulfotransferases"Xenobiotic Metabolism Disposition. 15(2). 171-176 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] S. Ozawa: "Relationship between genetic polymorphisms of drug metabolizing enzymes and disease susceptibility and drug responsiveness"Molecular Medicine. 38(10). 1146-1150 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Murayama, N., Ozawa, S.et al.: "Expression of CYP2A6 in Tumor cells augments cellular sensitivity to tegafur"Jpn. J. Cancer Res.. 92・5. 524-528 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sai, K., Ozawa, S.et al.: "A new metabolite of irinotecan in which formation is mediated by human hepatic cytochrome P450 3A4"Drug Metabol. Dispos.. 29・11. 1505-1513 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hanioka, N., Ozawa, S.et al.: "High performance liquid ehroma tographic assay for glucuronidation activity of SN-38 in human liver microsomes"Biomed. Chromatogr. 15・5. 328-333 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hanika, N., Ozawa, S.et al.: "Human liver UDP-glucuronosyltransferase isoforms involved in the glucuronidation of 7-ethhyl-10-hydroxycamptothecin"Xenobiotica. 31・10. 678-699 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nakamura, T., Ozawa, S.et al.: "Apparent low frequency in sequence variability in the proximal promoter region of captochrome P450(cyp)3A5 gene"Biol. Pharm. Bull. 24・8. 954-957 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 小澤正吾: "薬物代謝酵素の遺伝子多型と疾病感受性・薬物反応性の個体差"Molecular Medicine. 38・10. 1146-1150 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yang.M.,小澤正吾 ら: "Relationship Between NAT1 genetype and phenotype in a Japanese population"Pharmacogenetics. 10(3). 225-232 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] France,L.T.,小澤正吾 ら: "A simple colorimetric assay for phenotyping the major human thermostable phenol sulfotransfirase (SULTIAI) using platelet cytosols"Drug Motabolism Disposition. 28(9). 1063-1068 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 小澤正吾 ら: "Metabolic activation of o-phenyl phenol to a major cytotoxic metabolite phenylhydroquinone : role of human CYP1A2 and rat CYP2C11/CYP2E1"Xenobiotica. 30(10). 1005-1017 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nowell,S.,小澤正吾 ら: "Relationship of phenol sulfotransferase activity (SULTIAI) genotype to sulfotransferase phenotype in platelet uptosol"Pharmacogenetics. 10(9). 789-797 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 小澤正吾: "ヒト組織フェノール硫酸転移酵素の遺伝的多型性"薬物動態. 15(2). 171-176 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 小澤正吾 ら: "オーダーメード投薬"日本臨床. 59(1). 195-201 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] 小澤正吾 ら: "生物薬科学実験講座 第15巻"廣川書店. 280 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] 小澤正吾ら: "Analyses of bronchial bulky DNA adduct levels and CYP2C9,GSTP1,NQO1 genotypes in a Hungarian study population with pulmonary diseases"Carcinogenesis. 20(6). 991-995 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 小澤正吾ら: "Sulfating-activity and stability of cDNA-expressed allozymes of human phenolsulfotransferase,ST1A3^k1((^<213>Arg))and ST1A3^k2((^<213>His)),both of which exists in Japanese as well as Cancasians"J.Biochemistry(Tokyo). 126(2). 271-277 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 小澤正吾: "P450による代謝的活性化(毒性)"中毒研究. 12(4). 383-388 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 小澤正吾: "ヒト肝薬物代謝活性形質診断法の最近までの進歩"国立医薬品食品衛生研究所報告. 117. 63-79 (1999)

    • Related Report
      1999 Annual Research Report

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

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