Role of DNA adducts in hormonal carcinogenesis

In this review, a mechanism of estrogen-induced cancer has been examined which features a dual role of estrogen as hormone and carcinogen. Evidence exists that estrogens are metabolically activated to 4-hydroxylated metabolites by a specific cytochrome P450 in tissues prone to estrogen-induced cancer. These metabolites and their semiquinone/quinone oxidation products may cause various types of DNA damage. Preliminary data also exist that estrogens induce various genetic mutations. Tumors may develop from cells carrying such mutations and responding to receptor-mediated proliferation signals. (C) 2000 Academic Press.