Formaldehyde as a possible mutagenic metabolite of N-nitrodimethylamine and of other agents which are suggested to yield non-alkylating species in vitro

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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 His 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 [rat] 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 2 compounds. N-Nitromethylamine was not mutagenic with or without the metabolic activation system. Formaldehyde is possibly the mutagenically active intermediate formed during in vitro metabolism of N-nitrodimethylamine. The participation of formaldehyde as the mutagenic intermediate of other non-alkylating N-nitro and N-nitroso compounds is demonstrated.

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