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

植物雌激素对人类健康有益的生化和分子机制

• 批准号: 11672235
• 负责人: OZAWA Shogo
• 金额: $ 2.3万
• 依托单位: National Institute of Health Sciences
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11672235/
• 关键词: Estrogenicity; Human; Drug Metabolizing enzymes; Sulfotransferase; detoxification; gene expression; estrogen responsiveness; phytoestrogens; 代謝活性化

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.

在这项研究中，双酚A和植物雌激素，如染料木黄酮在人乳腺癌MCF-7细胞中的雌激素活性进行了比较，使用所谓的E-screen分析。我们还建立了诱导表达的pS2基因，一个雌激素反应基因，暴露后的MCF-7细胞的化学物质与雌激素。大豆苷元、柚皮素、山萘酚的雌激素活性较染料木素弱。对于雌激素类化合物的解毒途径，研究了人肝微粒体催化双酚A与植物雌激素的磺基结合反应。根据Km值，双酚A对磺基转移酶的亲和力似乎高于植物雌激素。ST 1A 3是一种热稳定的苯酚硫酸化磺基转移酶，被鉴定为双酚A硫酸化磺基转移酶，但植物雌激素与双酚A的雌激素作用机制尚不清楚。通过分析MCF-7细胞暴露于植物雌激素和双酚A（由于其雌激素作用而怀疑其毒性作用）后的基因表达，这是可能的。

项目成果

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)

S. Ozawa、M. Shimizu、Y. Matsumoto、M. Fukuoka、T. Katoh、Y. Ohno：“人体组织酚磺基转移酶的遗传多态性”异生物质代谢处置。

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)

Hanika, N., Ozawa, S. 等人：“参与 7-乙基-10-羟基喜树碱葡萄糖醛酸化的人肝脏 UDP-葡萄糖醛酸基转移酶异构体”Xenobiotica 31・10。

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"Pharmacogenetic

S. Nowell、C. B. Ambrosone、S. Ozawa、S. L. MacLeod、G. Mrackova、S. Williams、J. Plaxco、F. F. Kadlubar 和 N. P. Lang：“酚磺基转移酶活性 (SULT1A1) 基因型与血小板胞质中磺基转移酶表型的关系”药物遗传学

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)

Murayama, N., Ozawa, S.等：“肿瘤细胞中CYP2A6的表达增强细胞对替加氟的敏感性”Jpn. Cancer Res. 92・5 (2001)。

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)

小泽正吾：“药物代谢酶的遗传多态性以及疾病易感性和药物反应性的个体差异”《分子医学》38・10（2001）。