Inhibition of 2-fluorenamine-induced mutagenesis in Salmonella typhimurium by vitamin A.
Vitamin A alcohol (retinol) completely inhibited the mutagenicity of the carcinogen 2-fluorenamine (2-FA) in Salmonella typhimurium TA98 when the mutagen was activated by liver microsomes from CFN rats. The mutagenicity of 2-FA activated by 9,000Xg rat liver supernatant S9 was inhibited by retinol to a lesser degree. The decline in the number of his+ revertants was not an artifact due to bacterial killing, inasmuch as retinol was not toxic to the bacteria at levels that totally inhibited mutagenesis by 2-FA. Mutagenesis induced by adriamycin, an antibiotic that does not require metabolic activation for mutagenic potential, was unaffected by vitamin A. These results indicate that retinoids inhibit the metabolic activation of some chemical carcinogens to forms that can interact with DNA. Our findings are consistent with the hypothesis that retinoids may exert anticancer activity by inhibiting carcinogen activation, thereby inhibiting tumor induction. In addition to the more widely accepted role of retinoids in modulating the proliferation of epithelially derived neoplasms.
D000818:Animals; D001711:Biotransformation / Q000187:drug effects; D005449:Fluorenes / Q000037:antagonists & inhibitors* / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D009154:Mutation / Q000187:drug effects*; D051381:Rats; D012486:Salmonella typhimurium / Q000187:drug effects; D014801:Vitamin A / Q000494:pharmacology*
D005449:Fluorenes; D014801:Vitamin A; C012177:2-aminofluorene