Genotoxicity of Tamoxifen

Human Biomonitoring and Carcinogen Activation

Section: Section of Molecular Carcinogenesis

Studies on the carcinogenicity of the widely used anti-oestrogen tamoxifen have continued with investigations on the formation of tamoxifen–DNA adducts in different species and tissues. We have investigated the stereos electivity of metabolic activation of tamoxifen via one of its metabolites, a-hydroxy-N-desmethyltamoxifen and shown that the R-isomer forms more adducts in rat liver cells than the S-isomer. In contrast to the findings of others we have not detected the formation of adducts in human endometrium, despite using several highly sensitive methods. We therefore consider that tamoxifen is a non-genotoxic carcinogen to humans, in contrast to it being a genotoxic carcinogen in rats. We have prepared a quantified tamoxifen–DNA standard that is being used as a positive control to compare findings in interlaboratory collaborative investigations.