Mutagenicity of N-arylacetohydroxamic acids and their O-glucosides derived from chlorinated 4-nitrobiphenyl ethers.
The mutagenic activity of N-arylacetohydroxamic acids, their O-acetates, their O-glucosides, and N-arylhydroxylamines, derived from chlorinated 4-nitrobiphenyl ethers (CNBs), was tested in the Salmonella reversion assay. N-Arylhydroxylamines were mutagenic by themselves; however, other compounds containing an N-acetyl group showed mutagenic activity in the presence of guinea pig liver S9. The mutagenic activation of the glucosides of N-arylacetohydroxamic acids was caused by Ms but not by S10.5, whereas their aglycones, N-arylacetohydroxamic acids, were activated to mutagens by both the fractions. The mutagenic activation of these compounds was inhibited by bis(p-nitrophenyl)phosphate, which indicates that enzymatic deacetylation is a crucial step in the mutagenic activation. Analysis of metabolites of the O-glucosides of N-arylacetohydroxamic acids by h.p.l.c. indicates that the corresponding deacetylated O-glucosides are primary metabolites, which decomposed to amino and azoxy (via hydroxylamine) derivatives, and that the deacetylating activity of S9 locates exclusively in Ms.
D000818:Animals; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D005960:Glucosides / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D006027:Glycosides / Q000494:pharmacology*; D006168:Guinea Pigs; D006877:Hydroxamic Acids / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D009152:Mutagenicity Tests; D012486:Salmonella typhimurium / Q000187:drug effects*; D013329:Structure-Activity Relationship
D005960:Glucosides; D006027:Glycosides; D006877:Hydroxamic Acids