Accession Number : ADA332870

Title :   Analogs of Estrogen Metabolites as Probes of Estrogen-Induced Tumorigenesis

Descriptive Note : Annual rept. 1 Jul 96-30 Jun 97


Personal Author(s) : Bhat, Abhijit S.

PDF Url : ADA332870

Report Date : JUL 1997

Pagination or Media Count : 83

Abstract : Estrogens play a pivotal role in 50-60% of breast cancer case amongst females. Estrogen metabolites have been implicated as mediators in the development of estrogen-induced tumors. The catechol estrogens are particularly interesting chemically since they are prone to undergo further oxidative metabolism and form reactive intermediates like quinones, semiquinones and arene oxides. These reactive intermediates can undergo redox cycling in presence of the metal ions associated with cellular DNA and thereby produce a variety of Reactive Oxygen Species (ROS) like hydoxy, peroxy radicals and superoxide ions. The ROS produce cytotoxic and genotoxic effects in cells and tissues. Recently, 2-methoxyestradiol has been reported as a potent angiogenesis inhibitor via inhibition of tubulin polymerization. Thus, understanding the role of estradiol and its metabolites in estrogen-induced tumorigenesis will provide additional approaches to identify new targets for the development of therapies for prevention and treatment of hormone-dependent breast cancer. This predoctoral fellowship proposal focuses on interdisciplinary approaches to understanding the role of estrogen molecules in cancer development and the structural features critical for tumorigenesis. Chemical efforts are concentrating on the synthesis of catechol estrogens, homologs/mimics of catechol estrogens, and novel estrogen derivatives for probing the oxidative damage hypothesis. Biochemical approaches include the examination of estrogen metabolite formation in cell cultures, in vitro measurements of oxidative damage, and effects on tubulin polymerization.


Subject Categories : Medicine and Medical Research

Distribution Statement : APPROVED FOR PUBLIC RELEASE