PMID: 7034364Jan 1, 1981Paper

Metabolic activation and the mutagenic properties of carcinogenic N-nitramines in a liquid incubation test

Voprosy onkologii
V V KhudoleĭC Malaveille

Abstract

The study established the mutagenicity of carcinogenic dimethylnitramine and nitromorpholine in a liquid-incubation system using Salmonella typhimurium TA 100 and TA 1530 as indicator, in the presence of hepatic postmitochondrial supernatant obtained from 1254 aroclor-treated rats, oxygen and NADP+--generating system. Synthesis of mutagenic metabolites of nitramines was in correlation with the level of N-dimethylase activity. Ascorbic acid and disulfiram efficiently inhibited intramune-induced mutagenesis. Metabolic activation of nitramines involves (a) conversion of nitramines to nitrosoamines due to reduction of a nitro group, (b) hydroxylation by means of multi-function oxydases, and (c) heterolysis resulting in the formation of an end metabolite which is actually responsible for carcinogenicity and mutagenicity.

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