A study of 2,4,6-trinitrotoluene inhibition of benzo[a]pyrene uptake and activation in a microbial mutagenicity assay

A number of in vitro and in vivo studies have determined that binary and co mplex mixtures may interact to produce a toxicity that could not be predict ed based on the individual chemicals. The present study was conducted with a binary mixture of model compounds to investigate possible interactions af fecting their mutagenicity. The compounds included Benzo[a]pyrene (BAP), a polycyclic aromatic hydrocarbon that is an indirect-acting mutagen of great environmental concern, and 2,4,6-Trinitrotoluene (TNT), a nitro-aromatic c ompound that is a direct-acting mutagen frequently found as a soil contamin ant at munitions sites. This study indicated that a binary mixture of BAP a nd TNT failed to induce the positive mutagenic response in Salmonella typhi murium strain TA98 characteristic of either compound alone. Spectrofluorome tric analysis of BAP, and kinetic analyses of (3)HBAP uptake in the presenc e or absence of TNT using TA98 cells that were treated or untreated with ac tivated rat liver microsomes were performed. In cells preloaded with BAP, c ellular BAP fluorescence was rapidly suppressed in the presence of TNT. Mas s spectroscopy of BAP and TNT mixtures revealed a. number of products, beli eved to be the result of complexation and nitration, that may account for t he antagonistic action of TNT on BAP-induced mutagenicity in TA98 cells. Fu rther, kinetic studies indicated that TNT inhibited the incorporation of BA P into cells. (C) 2001 Elsevier Science Ltd. All rights reserved.