Biochemical and molecular mechanisms of beneficial effects for human health by phytoestrogens
Biochemical and molecular mechanisms of beneficial effects for human health by phytoestrogens
批准号:
11672235
负责人:
OZAWA Shogo
金额:
$2.3万
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
项目状态:
已结题
起止时间:
1999 至 2001
中文摘要
在这项研究中,双酚A和植物雌激素,如染料木素,比较了雌激素对人乳腺癌MCF-7细胞的雌激素活性。我们还建立了在MCF-7细胞暴露于具有雌激素活性的化学物质后,诱导雌激素应答基因PS2基因的表达。大豆苷元、柚皮素、山奈酚的雌激素活性弱于染料木素。对于雌激素类化合物的解毒途径,双酚A和植物雌激素的磺化偶联反应是由人肝微粒体催化的。在Km值的基础上,双酚A对磺基转移酶的亲和力似乎高于植物雌激素。一种耐热的苯酚-磺化转移酶ST1A3被鉴定为双酚A-磺化转移酶。然而,植物雌激素和双酚A在雌激素作用机制上没有差别。通过分析MCF-7细胞暴露于植物雌激素和双酚A后的基因表达是可能的,双酚A的毒性作用被怀疑是由于其雌激素作用。
英文摘要
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.
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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。
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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。
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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
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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)。
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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)。
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