ROLE OF CATECHOL FORMATION IN ESTROGEN-MEDIATED CANCER

非蛋白结合雌二醇相关性的流行病学研究 患乳腺癌的妇女的血清水平提供了 我们对生物形成的基础研究的理论基础 雌激素介导的癌症中雌二醇的活化代谢产物。乳房 癌症被认为是由激素调节的，雌激素被认为是 成为肿瘤表达的首要因素。这项研究的目的是 计划是确定儿茶酚雌激素形成在 雌激素介导的癌症。我们的工作假设是致癌物质 雌激素的潜力将与它们的代谢率相关。 对儿茶酚的激活，但与其荷尔蒙无关 活动。对这一假说的支持是由In Balb/c 3T3细胞亚克隆及其来源的体外肿瘤转化 叙利亚仓鼠肝细胞致癌性的体内检测。一个 由四个结构相关的化合物组成的一组，由两个荷尔蒙 活性雌激素和两种激素不活性的衍生物将提供 支持我们中心假设的证据。一项重大贡献 这项计划将发现一种具有激素活性的非致癌物质 雌激素。如果我们的体外结果得到了来自In的证据支持 活体模型系统，它将提供疑似机制的确认 与内源性非蛋白结合相关的致癌作用 血清雌二醇水平和治疗性雌激素的作用。

Epidemiological studies on the association of nonprotein-bound estradiol levels in serum from women who developed breast cancer provide the rationale for our basic investigation of the formation of biologically activated metabolites of estradiol in estrogen-mediated cancer. breast cancer is considered to be hormonally mediated, and estrogens are believed to be the prime agents in tumor expression. The objective of this research program is to establish the role of catechol estrogen formation in estrogen-mediated cancer. Our working hypothesis is that the carcinogenic potential of estrogens will correlate with their rates of metabolic activation to catechols, but will not be related to their hormonal activity. Support for this hypothesis is provided by results from the in vitro neoplastic transformation of a subclone of Balb/c 3T3 cells and from an in vivo assay for hepatocellular carcinogenicity in Syrian hamsters. A group of four structurally related compounds composed of two hormonally active estrogens and two hormonally inactive derivatives will provide evidence to support our central hypothesis. A significant contribution of this program will be the discovery of a hormonally active noncarcinogenic estrogen. If our in vitro results are supported by evidence from the in vivo model system, it will provide confirmation of a suspected mechanism involved in carcinogenesis associated with endogenous nonprotein bound serum estradiol levels and the effects of therapeutic estrogens.