MUTAGENIC ACTIVITY OF 2,4,6-TRINITROTOLUE NE - THE ROLE OF METABOLIZING ENZYMES

Mutagenic activity of 2,4.6-trinitrotoluene (2,4,6-TNT) and one of its derivatives, 2,4-diamino-6-nitrotoluene (2,4-DA-6-NT) was studied in the Ames test using the Salmonella typhimurium tester strains TA98, TA 100, TA100NR (deficient in classical nitroreductases), and TA100/1,8DN P (deficient in 0-acetyltransferase). The number of revertants was sig nificantly increased by 2,4,6-TNT, in comparison with that of spontane ous revertants. Base pair substitutions were preferentially induced by 2,4,6-TNT. The mutagenic effect of this compound was virtually altere d by in vitro metabolic activation with the S9 fraction of human place nta. Neither 2,4,6-TNT nor 2,4-DA-6-NT exhibited mutagenic activity in the strains TA100NR and TA100/1,8DNP. Based on the results obtained, it is concluded that the mutagenic potential of 2,4,6-TNT is determine d by its metabolites that form during bacterial metabolism. Bacterial nitroreductases and 0-acetyltransferases are the key activators of thi s compound to form the ultimate mutagens.