DNA adducts caused by tamoxifen and toremifene in human microsomal system and lymphocytes in vitro

DNA-binding of tamoxifen and toremifene was studied in rat in vivo, in human and rat microsomes in vitro, and in cultured primary human lymphocytes by 32P-postlabelling. Only tamoxifen caused DNA adducts in rat liver. Both compounds induced adducts in both rat and human microsomal systems and in cultured lymphocytes. The levels of adducts in microsomes and lymphocytes were low, ca. 1 adduct/10(9) nucleotides. Toremifene showed lower binding in each system, and in lymhocytes adducts were only detected at a cytotoxic dose level.