Mutagenicity of N-hydroxy-2-acetylaminofluorene and N-hydroxy-phenacetin and their respective deacetylated metabolites in nitroreductase deficient Salmonella TA98FR and TA100FR.
The mutagenicity of N-hydroxy-2-acetylaminofluorene and N-hydroxyphenacetin and their respective deacetylated metabolites, N-hydroxy-2-aminofluorene and 2-nitrosofluorene, and N-hydroxyphenetidine and rho-nitrosophenetole was determined in nitroreductase deficient Salmonella tester strains TA 98FR and TA100FR. The mutagenicity of N-hydroxy-2-acetylaminofluorene medicated by either rat liver microsomes or rat liver 105 000 g supernatant fractions was no different in either TA98 (nitroreductase proficient) or TA98FR (nitroreductase deficient). Similarly the mutagenicity of N-hydroxyphenacetin mediated by hamster liver microsomes was not affected by either the presence or absence of nitroreductase activity in TA100. N-Hydroxy-2-aminofluorene and 2-nitrosofluorene were equipotent direct acting mutagens in both TA98 and TA98FR, as were both N-hydroxyphenetidine and rho-nitrosophenetole in TA100 and TA 100FR. Ascorbate (5 mM) and NADPH (1 mM) had no significant effect on the mutagenicity of either N-hydroxy-2-acetylaminofluorene, N-hydroxy-2-aminofluorene, or 2-nitrosofluorene in TA98 or TA98FR whereas ascorbate and NADPH markedly inhibited the mutagenicity of both N-hydroxyphenetidine and rho-nitrosophenetole in both TA100 and TA100FR. Ascorbate appears to be inhibiting the mutagenicity of N-hydroxyphenetidine and rho-nitrosophenetole as a result of the nonenzymatic chemical reduction of these compounds to non-mutagenic derivatives.
D015073:2-Acetylaminofluorene / Q000031:analogs & derivatives*; D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D006224:Cricetinae; D006881:Hydroxyacetylaminofluorene / Q000378:metabolism / Q000633:toxicity*; D008297:Male; D008647:Mesocricetus; D008862:Microsomes, Liver / Q000378:metabolism; D009152:Mutagenicity Tests; D009154:Mutation; D009574:Nitro Compounds / Q000378:metabolism; D009601:Nitroreductases; D010088:Oxidoreductases / Q000378:metabolism; D010615:Phenacetin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains; D012475:Salmonella / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics
D009574:Nitro Compounds; C008068:N-hydroxyphenacetin; D006881:Hydroxyacetylaminofluorene; D015073:2-Acetylaminofluorene; D010088:Oxidoreductases; D009601:Nitroreductases; D010615:Phenacetin; D001205:Ascorbic Acid