Inhibition of 7,12-dimethylbenz[a]anthracene-induced genotoxicity in Chinese hamster ovary cells by retinol and retinoic acid.
The effects of retinol and retinoic acid on cytotoxicity and mutation expression at the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) locus in Chinese hamster ovary (CHO) cells with or without exogenous metabolic activation were studied in the presence and absence of known chemical mutagens. Neither retinol nor retinoic acid induced mutants at the HGPRT locus of CHO cells at concentrations ranging from 1 microM to 50 microM without exogenous metabolic activation, and at concentrations ranging from 1 microM to 25 microM in the presence of Aroclor 1254-induced rat liver S9. Retinol and retinoic acid did not affect 100 micrograms/ml ethyl methanesulfonate-induced cytotoxicity or mutations at the HGPRT locus of CHO cells in the absence of exogenous metabolic activation at concentrations ranging from 1 microM to 25 microM. In contrast, retinol and retinoic acid inhibited 7,12-dimethylbenz[a]anthracene-induced cytotoxicity and mutation induction at the HGPRT locus of CHO cells when either uninduced Sprague-Dawley rat liver S9, Aroclor 1254-induced Sprague-Dawley rat liver S9 or co-cultivated primary Sprague-Dawley rat hepatocytes were used to provide metabolic activation. These data show that retinoids are capable of inhibiting mutation induction in mammalian cells in vitro by a chemical promutagen requiring metabolic activation to a reactive form, and suggest that such inhibition is due to an alteration of mutagen metabolism.
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000037:antagonists & inhibitors*; D000818:Animals; D001711:Biotransformation; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D004249:DNA Damage; D005020:Ethyl Methanesulfonate / Q000037:antagonists & inhibitors; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D008862:Microsomes, Liver / Q000378:metabolism; D009152:Mutagenicity Tests; D009154:Mutation / Q000187:drug effects; D051381:Rats; D014212:Tretinoin / Q000494:pharmacology*; D014801:Vitamin A / Q000494:pharmacology*
D014801:Vitamin A; D014212:Tretinoin; D015127:9,10-Dimethyl-1,2-benzanthracene; D005020:Ethyl Methanesulfonate; D007041:Hypoxanthine Phosphoribosyltransferase