Genotoxic activity of nitroaromatic explosives and related compounds in Salmonella typhimurium.
A number of nitroaromatic explosives and related compounds were examined for mutagenic activity with the Salmonella/mammalian microsome test. 9 of 11 nitroaromatics tested were mutagenic, including 2,4,6-trinitrotoluene, the most widely produced military explosive. All the nitroaromatics, except 2,4,6-trinitrophenol and 2,3,5-trinitroresorcinol, were at least an order of magnitude more mutagenic than 3 dinitrotoluene (DNT) isomers. The most active compound was 2,3,5-trinitronaphthalene, which was approximately 5000 times more mutagenic than DNT isomers. These compounds induced predominantly frameshift mutations. The mutagenic activity did not require S9 activation, but was largely dependent on the presence of an intact nitroreductase capability in the test bacteria. This implied that reduced metabolites, possibly hydroxylamines, are the proximal mutagenic intermediates.
D000818:Animals; D001711:Biotransformation; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D009154:Mutation; D009578:Nitrobenzenes / Q000633:toxicity*; D009601:Nitroreductases; D010088:Oxidoreductases / Q000378:metabolism; D051381:Rats; D012486:Salmonella typhimurium / Q000187:drug effects; D013045:Species Specificity; D013329:Structure-Activity Relationship
D009153:Mutagens; D009578:Nitrobenzenes; D010088:Oxidoreductases; D009601:Nitroreductases