Retinol (vitamin A) inhibition of dimethylnitrosamine (DMN) and diethylnitrosamine (DEN) induced sister-chromatid exchanges in V79 cells and mutations in Salmonella/microsome assays.
When the Chinese hamster cell line V79 and the tester strain of Salmonella typhimurium TA100 were treated with the precarcinogens dimethylnitrosamine (DMN) or diethylnitrosamine (DEN) in the presence of S9 mix, a dose-dependent increase of sister-chromatid exchanges (SCE) in V79 cells and His+ revertants in TA100 resulted. DMN was a far more efficient SCE inducer than DEN, while DEN was a more efficient inducer of His+ revertants than DMN. Retinol (Rol) effectively inhibited DMN and DEN induced SCE in V79 cells and His+ revertants in TA100. Concurrent treatment of V79 cells with Rol at various doses and one dose of DMN or DEN in the presence of S9 mix caused a significant reduction of SCE as compared to SCE induced by DMN or DEN without Rol. Rol inhibition of DMN-induced SCE was dose-dependent. Rol was less efficient in inhibiting DEN-induced SCE, and no consistent dose-dependent inhibition was observed. At all doses, Rol significantly inhibited DMN and DEN induced mutation frequencies in TA100. At the highest dose of Rol (40 micrograms/plate), the inhibition of DMN and DEN induced His+ revertants reached about 90% and 60%, respectively. The possibility that Rol exerts its antimutagenic activities by inhibiting certain forms of the cytochrome P-450 isoenzymes required for activation of precarcinogens such as DMN and DEN is discussed.
D000818:Animals; D001711:Biotransformation; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D004052:Diethylnitrosamine / Q000494:pharmacology* / Q000633:toxicity; D004128:Dimethylnitrosamine / Q000494:pharmacology* / Q000633:toxicity; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism; D009152:Mutagenicity Tests; D009153:Mutagens; D009154:Mutation; D012486:Salmonella typhimurium / Q000187:drug effects; D012854:Sister Chromatid Exchange / Q000187:drug effects*; D014801:Vitamin A / Q000494:pharmacology*
D009153:Mutagens; D014801:Vitamin A; D004052:Diethylnitrosamine; D004128:Dimethylnitrosamine