Understanding the genotoxicity of tamoxifen?

Tamoxifen is an anti-oestrogenic drug widely used for adjuvant therapy of breast cancer. Its use has caused an increased incidence of endometrial cancer and it is also a potent carcinogen in rat liver. Since the demonstration that tamoxifen forms covalent DNA adducts in rat liver, many investigations of its mechanism of carcinogenic action have focused on the examination of human and animal tissues for the presence of tamoxifen-DNA adducts, the identification of their structures and the determination of the metabolic pathways that lead to their formation. This article reviews the current evidence for genotoxic mechanisms for tamoxifen carcinogenicity, and discusses some inconsistencies in the data.