DNA adduct formation of selected sex steroids in human liver slices in vitro

Toxicology in Vitro : an International Journal Published in Association with BIBRA
W FeserW Kuhnz

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 (32)P-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>CMAMPA. The DNA adduct levels varied inter-individually. At a treatment concentration of 1mug/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 incubati...Continue Reading

References

Jan 16, 1987·Science·J M Bishop
Jan 1, 1996·Drug Safety : an International Journal of Medical Toxicology and Drug Experience·T RabeB Runnebaum
Jul 1, 1996·Human & Experimental Toxicology·W FeserR Reimann
May 1, 1997·Pharmacoepidemiology and Drug Safety·L A HeinemannUNKNOWN Collaborating Centers

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Citations

Nov 25, 2000·Toxicology·C Lerche-Langrand, H J Toutain
Dec 5, 2002·Mutation Research·Giovanni Brambilla, Antonietta Martelli
Aug 29, 2007·Clinics in Liver Disease·Edmundo A Rodriguez-Frias, William M Lee
Nov 8, 2012·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Brian G Lake, Roger J Price
Sep 13, 2019·Endocrine Reviews·Britton TrabertFrank Z Stanczyk

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