Mutagenicity of the phenacetin metabolites: N-hydroxy-p-phenetidine and nitrosophenetol in S. typhimurium TA100 and derivatives deficient in nitroreductase or O-acetylase: probes for testing intrabacterial metabolic activation.
Two mutagenic metabolites of phenacetin, p-nitrosophenetol and N-hydroxy-p-phenetidine, were tested in S. typhimurium strains TA100, its nitroreductase-deficient derivative TA100NR, and O-acetylase-deficient strains TA100 Tn5-1,8-DNP1011 and -DNP1012 in the presence or absence of an exogenous metabolic activation system. The results indicate that bacterial nitroreductase(s) and O-acetylase(s), shown to be involved in the conversion of certain nitroarenes, are not required for the intrabacterial activation of the two phenacetin metabolites to bacterial mutagens. In view of the low reactivity of nitrosoarenes towards nucleophiles at neutrality, the mechanism by which they exert such a high mutagenic effect in S. typhimurium strains remains to be clarified, but is discussed.
D000115:Acetylesterase / Q000172:deficiency; D000627:Aminophenols / Q000633:toxicity*; D001711:Biotransformation; D009152:Mutagenicity Tests; D009153:Mutagens; D009154:Mutation; D009601:Nitroreductases; D010088:Oxidoreductases / Q000172:deficiency; D010615:Phenacetin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000633:toxicity; D010628:Phenetidine / Q000031:analogs & derivatives / Q000378:metabolism / Q000633:toxicity*; D012486:Salmonella typhimurium / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism
D000627:Aminophenols; D009153:Mutagens; D010628:Phenetidine; C001412:2-hydroxyphenetidine; C037221:4-nitrosophenetole; D010088:Oxidoreductases; D009601:Nitroreductases; D000115:Acetylesterase; D010615:Phenacetin