Effect of retinoids on carcinogen-induced mutagenesis in Salmonella tester strains.
The ability of retinol (Rol) in altering mutation frequencies induced by 7 carcinogens was studied in Salmonella/microsome assay using 4 tester strains namely TA98, TA100, TA102 and TA1535. The 7 carcinogens used were aflatoxin B1 (AFB), cyclophosphamide (CPP), 3-methylcholanthrene (MCA), benzo[a]pyrene (BP), benz[a]anthracene (BA), 9,10-dimethyl-1,2-benz[a]anthracene (DMBA) and mitomycin C (MMC). As reported previously, Rol significantly reduced the number of His+ revertants induced by AFB. It also reduced mutations induced by CPP or MCA but not that by BP, BA, DMBA or MMC. The abilities of Rol, retinoic acid, retinyl acetate and a known inhibitor for certain P-450 isozymes, 7,8-benzoflavone (BF) in inhibiting mutations caused by AFB and BP were studied and compared. All the 3 retinoids caused significant reduction of AFB-induced His+ revertants in a dose-dependent manner, but there was no effect on BP-induced mutation. BF strongly inhibited both AFB- and BP-induced revertants. The possibility of retinoids in exerting their effects on mutagenesis of precarcinogens by inhibiting only certain forms of cytochrome P-450 enzymes is discussed.
D000818:Animals; D001711:Biotransformation / Q000187:drug effects; D002273:Carcinogens / Q000037:antagonists & inhibitors / Q000633:toxicity*; D065607:Cytochrome P-450 Enzyme Inhibitors; D009152:Mutagenicity Tests; D009154:Mutation / Q000187:drug effects*; D051381:Rats; D012176:Retinoids / Q000494:pharmacology*; D012486:Salmonella typhimurium / Q000187:drug effects; D014801:Vitamin A / Q000494:pharmacology
D002273:Carcinogens; D065607:Cytochrome P-450 Enzyme Inhibitors; D012176:Retinoids; D014801:Vitamin A