Peroxidase-mediated dealkylation of tamoxifen, detected by electrospray ionization-mass spectrometry, and activation to form DNA adducts

► Tamoxifen (TAM) is extensively used for treatment and prevention of breast cancer. ► TAM treatment causes ~ 2- to 8-fold increase in risk of endometrial cancer. ► We used UPLC-MS/MS to investigate peroxidase mediated TAM metabolism and DNA adducts. ► Results show dealkylation of TAM and further activation to form DNA adducts. ► We propose similar molecular reactions in endometrium could lead to carcinogenicity.