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

异黄酮型植物雌激素被认为可以预防激素依赖型癌症，例如乳腺癌和前列腺癌，但这些有益作用的机制仍然不清楚。一个可能的机制是异黄酮干扰内源性雌激素17b-雌二醇的代谢激活和失活。这种代谢干扰将在来自雌性ACI大鼠肝脏、雄性叙利亚仓鼠肝脏和雄性叙利亚仓鼠肾脏的精切组织切片中进行研究，叙利亚仓鼠肾脏是雌二醇致癌的靶器官。DNA损伤和细胞的氧化状态将在相同的组织中进行研究，并与异黄酮类和雌二醇单独或联合代谢相关。还将确定分别负责植物雌激素和雌二醇羟化和葡萄糖醛酸化的细胞色素P450和UDP-葡萄糖醛酸基转移酶的异构体。拟议的研究结果应该有助于更好地了解异黄酮类植物雌激素的有益作用，并提供关于异黄酮类可能的遗传毒性潜力的信息。

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.