Effects of Dietary Isoflavones on the Metabolism and Genotoxicity of 17ß-Estradiol in vitro

• Applicant: Professor Dr. Manfred Metzler
• Subject Area: Nutritional Sciences
• Term: from 2003 to 2006
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5402231

Phytoestrogens of the isoflavone type are believed to protect against hormone-dependent cancer, e.g. of the breast and prostate, but the mechanisms of these beneficial effects remain elusive. One possible mechanism could be that isoflavones interfere with the metabolic activation and inactivation of the endogenous estrogen 17b-estradiol. This metabolic interference will be studied in precision-cut tissue slices from female ACI rat liver, male Syrian hamster liver and male Syrian hamster kidney, a target organ of estradiol carcinogenicity. DNA damage and the oxidative status of the cells will be investigated in the same tissues and correlated with the metabolism of the isoflavones and estradiol alone and in combination. The isoforms of cytochrome P450 and UDP-glucuronosyltransferase responsible for the hydroxylation and glucuronidation, respectively, of the phytoestrogens and estradiol will also be determined. The results of the proposed study should lead to a better understanding of the beneficial effects of isoflavone phytoestrogens and provide information about a possible genotoxic potential of isoflavones.

• DFG Programme: Research Grants