Studies for a genotoxic potential of some endogenous and exogenous sex steroids. I. Communication: examination for the induction of gene mutations using the Ames Salmonella/microsome test and the HGPRT test in V79 cells.
The mutagenicity results and data of nine progestins (cyproterone acetate, dehydrospirorenone, gestodene, gestonorone caproate, levonorgestrel, norethisterone, norethisterone acetate, norethisterone enanthate, norethynodrel), one hypothetical metabolite (6,7-epoxy-cyproterone acetate), four estrogens (estradiol, ethinylestradiol, cyclodiol, cyclotriol), and four other sex steroids (atamestane, lilopristone, onapristone, propylmesterolone) are reported. All 17 sex steroids were investigated using the Ames salmonella/microsome direct plate incorporation protocol, and seven were additionally tested using the preincubation modification. Seven sex steroids were also studied in the HG-PRT test with V79 cells for the induction of gene mutations in mammalian cells. The metabolite was examined in the Ames salmonella/microsome assay using the standard protocol and the preincubation modification. In all assays the test compounds were investigated up to concentration levels where cytotoxicity and/or visible precipitation occurred or at least the solubility limit of the test compound was reached. For all assays, evaluation of the data indicates that neither any of the sex steroids nor the hypothetical metabolite was able to induce gene mutations whether in the absence or the presence of an extrinsic metabolizing system (S9 mix).
Lang
R
R
Schering AG, Institute of Experimental Toxicology, Berlin, Germany.
Reimann
R
R
D000818:Animals; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D017373:Cyproterone Acetate / Q000031:analogs & derivatives; D004852:Epoxy Compounds / Q000633:toxicity; D004958:Estradiol / Q000633:toxicity; D045166:Estradiol Congeners / Q000633:toxicity*; D012739:Gonadal Steroid Hormones / Q000633:toxicity*; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D008110:Liver Extracts; D008861:Microsomes / Q000201:enzymology; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D011372:Progestins / Q000633:toxicity*; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D013256:Steroids / Q000633:toxicity
D004852:Epoxy Compounds; D045166:Estradiol Congeners; D012739:Gonadal Steroid Hormones; D008110:Liver Extracts; D009153:Mutagens; D011372:Progestins; D013256:Steroids; D017373:Cyproterone Acetate; D004958:Estradiol; D007041:Hypoxanthine Phosphoribosyltransferase