Mutagenic and DNA-damaging effects of N-alkyl-N-(alpha-acetoxyalkyl)nitrosamines, models for metabolically activated N,N-dialkylnitrosamines.
Mutagenic and DNA-damaging effects of a series of N,N-dialkylnitrosamines monosubstituted at the alpha-carbon with an acetoxyl group were tested in Salmonella typhimurium, Escherichia coli, and Bacilus subtilis in the absence of metabolic activation system. The compounds comprised 8 N-alkyl-N-(acetoxymethyl)nitrosamines (alkyl=methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, or tert-butyl) and N-butyl-N-(1-acetoxybutyl)nitrosamine. All the compounds, except one with a tert-butyl group, gave positive results in these mutagenicity and repair tests. Presumed release of alkyl cations from the corresponding alpha-acetoxy derivatives by hydrolysis and heterolysis caused mutagenic and DNA-damaging effects in the bacteria. Structure-activity correlation of the compounds was noted in these tests and discussed in regard to the mutagenicity with metabolic activation and carcinogenicity of N,N-dialkylnitrosamines. The results support the hypothesis that alpha-carbon hydroxylation is one probable mechanism involved in the metabolic activation of N,N-dialkylnitrosamines.
D001412:Bacillus subtilis / Q000187:drug effects; D004260:DNA Repair / Q000187:drug effects; D004269:DNA, Bacterial / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D008954:Models, Biological; D009153:Mutagens; D009602:Nitrosamines / Q000494:pharmacology*; D012486:Salmonella typhimurium / Q000187:drug effects
D004269:DNA, Bacterial; D009153:Mutagens; D009602:Nitrosamines