The effect of biotransformation of 2,4-dinitrotoluene on its mutagenic potential.
Because both oxidative and reductive metabolism of the hepatocarcinogen 2,4-dinitrotoluene (2,4-DNT) can occur in vivo, we have examined the mutagenicity of compounds which can be formed from 2,4-DNT in an attempt to establish which metabolic pathways contribute to the formation of genotoxic products. A quantitative reversion assay using Salmonella typhimurium TA98 was used to evaluate the mutagenicity of these compounds. 2,4-Dinitrobenzyl alcohol, 2-amino-4-nitrotoluene and 2-nitroso-4-nitrotoluene were found to be more mutagenic to S. typhimurium than is 2,4-DNT and did not require metabolic activation by post-mitochondrial supernatants of Aroclor-induced rat liver homogenates (S9) for their effect. 2-Amino-4-nitrobenzoic acid was also mutagenic to S. typhimurium TA98 in the absence of S9, but its mutagenicity was enhanced when S9 was included in the incubation mixture. 2,4-Diaminotoluene required S9 for demonstration of mutagenicity and was approximately as effective, on a molar basis, as 2,4-DNT in inducing reversion to histidine prototrophy. These results suggest that both oxidative and reductive metabolism may be involved in production of mutagenic metabolites of 2,4-DNT.
Couch
D B
DB
Chemical Industry Institute of Toxicology, Research Triangle Park, NC 27709.
Abernethy
D J
DJ
Allen
P F
PF
D000818:Animals; D001711:Biotransformation; D004136:Dinitrobenzenes / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D009153:Mutagens / Q000378:metabolism*; D009154:Mutation; D009578:Nitrobenzenes / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats; D011916:Rats, Inbred F344; D012486:Salmonella typhimurium / Q000187:drug effects
D004136:Dinitrobenzenes; D009153:Mutagens; D009578:Nitrobenzenes; C016403:2,4-dinitrotoluene