Mechanisms of Tamoxifen-Induced Genotoxicity and Carcinogenicity
Tamoxifen is an anti-estrogen widely used with proven efficacy in the treatment of breast cancer in women (1). It is well tolerated and has potentially beneficial actions in reducing serum cholesterol (2) and the incidence of fatal heart attacks (3). Preliminary results suggest that tamoxifen will reduce the incidence of breast cancer in such women (2). However, several epidemiological studies in women with breast cancer have shown that tamoxifen can also lead to increased incidence of endometrial tumors (4–6). Although tamoxifen is primarily an antiestrogen, it also has some estrogenic properties. At present, it is not clear whether the effect on the endometrium is due to estrogen-like stimulation by tamoxifen, causing cell proliferation and the promotion of endogenous lesions, or a direct mutagenic effect on the affected cells.
KeywordsEstrogen Glutathione Adduct Testosterone NADPH
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