[Metabolic activation and the mutagenic properties of carcinogenic N-nitramines in a liquid incubation test].
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.
D000814:Aniline Compounds / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D002273:Carcinogens / Q000378:metabolism* / Q000494:pharmacology; D004048:Diethylamines / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D004123:Dimethylamines / Q000378:metabolism / Q000494:pharmacology; D004221:Disulfiram / Q000494:pharmacology; D005260:Female; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D009025:Morpholines / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D009152:Mutagenicity Tests; D009153:Mutagens / Q000378:metabolism* / Q000494:pharmacology; D009578:Nitrobenzenes / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D012486:Salmonella typhimurium / Q000187:drug effects / Q000378:metabolism
D000814:Aniline Compounds; D002273:Carcinogens; D004048:Diethylamines; D004123:Dimethylamines; D009025:Morpholines; D009153:Mutagens; D009578:Nitrobenzenes; C031405:N-nitromorpholine; C031406:N-nitrodiethylamine; C015384:nitramine; C013962:dimethylnitramine; D001205:Ascorbic Acid; D004221:Disulfiram
Metabolicheskaia aktivatsiia i mutagennye svoĭstva kantserogennykh N-nitraminov v zhidkostno-inkubatsionnoĭ probe.