DNA Adduct Formation of Selected Sex Steroids in Human Liver Slices In Vitro

Abstract

We report investigations into the potential of the steroid hormones chlormadinone acetate (CMA), cyproterone acetate (CPA), dexamethasone (DEX), estradiol (E 2), ethinylestradiol (EE 2), gestodene (GEST), levonorgestrel (LNG), megestrol acetate (MGA), medroxy progesterone acetate (MPA), mifepristone (MIFE), norethisterone (NET), prednisolone (PRED), progesterone (P) and testosterone (T) to form DNA adducts in precision-cut human liver slices in vitro from 14 male and female donors using the 32P-postlabelling technique. The synthetic steroid hormones CPA, CMA and MGA generated DNA adducts in human liver slices obtained from all donors. MPA-related adduct spots were only observed in some of the livers tested. No DNA adduct formation was detectable with DEX, EE 2, E 2, GEST, LNG, MIFE, NET, PRED, P and T. The total DNA adduct levels and adduct patterns were different for each compound. On average, total DNA adduct levels decreased in the following order: CPA>MGA>CMA⪢MPA. The DNA adduct levels varied inter-individually. At a treatment concentration of 1 μg/ml, the coefficient of variation of the total adduct levels ranged from 38% to 101%. A sex-specific distribution of the DNA adduct formation was only detected after incubation with MPA. MPA-related adduct spots were observed predominantly in the livers of female donors.