title: Formaldehyde as a possible mutagenic metabolite of N-nitrodimethylamine and of other agents which are suggested to yield non-alkylating species in vitro.
abstract: N-Nitramines are biologically active compounds of environmental significance. In this study the suggested bioactivation of N- nitrodimethylamine via oxidation at the methyl-group was confirmed, as was indicated by formaldehyde liberation. N- Nitrodimethylamine and formaldehyde as well as the suggested metabolites, N- nitrohydroxymethylmethylamine and N- nitromethylamine were tested for mutagenicity in histidine auxotrophic Salmonella typhimurium strains in a variety of conditions. N- Nitrodimethylamine was mutagenic only in S. typhimurium TA 100 after pre-incubation with bacteria and a complete metabolizing mixture containing 9000 g liver supernatant and NADPH-regenerating cofactors. N- Nitrohydroxymethylmethylamine and formaldehyde were approximately equally mutagenic without the metabolizing mixture in TA 100 and TA 98, but not in TA 1535. The addition of the 9000 g supernatant of homogenized liver increased the yield of his+ revertants induced by the two compounds. N- Nitromethylamine was not mutagenic with or without the metabolic activation system. The results suggest that formaldehyde is possibly the mutagenically active intermediate formed during in vitro metabolism of N- nitrodimethylamine . Furthermore the participation of formaldehyde as the mutagenic intermediate of other non-alkylating N-nitro and N-nitroso compounds is demonstrated.
mesh_terms: D000818:Animals; D001711:Biotransformation; D002273:Carcinogens / Q000378:metabolism*; D004123:Dimethylamines / Q000378:metabolism* / Q000633:toxicity; D005557:Formaldehyde / Q000378:metabolism / Q000633:toxicity*; D008862:Microsomes, Liver / Q000378:metabolism*; D009152:Mutagenicity Tests; D009153:Mutagens; D009154:Mutation; D051381:Rats; D011919:Rats, Inbred Strains; D012486:Salmonella typhimurium / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D002273:Carcinogens; D004123:Dimethylamines; D009153:Mutagens; D005557:Formaldehyde; C013962:dimethylnitramine