Mutagenicities of 2,4- and 2,6-dinitrotoluenes and their reduced products in Salmonella typhimurium nitroreductase- and O-acetyltransferase-overproducing Ames test strains

Mutagenicities of 2,4- and 2,6-dinitrotoluene (2,4-and 2,6-DNT), and reduce d metabolites formed by the incubation of 2,4- and 2,6-DNT with Salmonella typhimurium TA98, were tested using S. typhimurium YG strains possessing hi gh level of nitroreductase (NR) and/or O-acetyltransferase (OAT) activities . All compounds tested showed greatest mutagenic activities toward strains YG1041 and YG1042, which possess high levels of NR and OAT activities. The relative mutagenic activities of 2,4-DNT and its related compounds toward Y G1041 and YG1042 were aminonitrotoluenes (2A4NT, 4A2NT) < 2,4-DNT < 2,2'-di methyl-5,5'-dinitroazoxybenzene (2,2'-DM-5,5'-DNAOB) =4-hydroxylamino-2-nit rotoluene (4HA2NT) << 4,4'-dimethyl-3,3'-dinitroazoxybenzene (4,4'-DM-3,3'- DNAOB), and aminonitrotoluenes (2A4NT, 4A2NT) < 2,4-DNT < 4HA2NT=4,4'-dimet hyl-3,3'-dinitroazoxybenzene (4,4'-DM-3,3'-DNAOB) < 2HA4NT, respectively. I n addition, the relative mutagenic activities of 2,6-DNT and its related co mpounds toward YG1041 and YG1042 were 2,6-DNT < 2-hydroxylamino-6-nitrotolu ene (2HA6NT) < 2,2'-dimethyl-3,3'-dinitroazoxybenzene (2,2'-DM-3,3'-DNAOB), and 2-amino-6-nitrotoluene (2A6NT) < 2,6-DNT < 2HA6NT, respectively. These results, together with previous findings, suggested that aminohydroxylamin o dimethylazoxybenzenes or aminohydroxylamino dimethylazobenzenes produced either by the reduction of hydroxylaminonitrotoluenes or by the reduction o f dimethyl dinitroazoxybenzenes are active metabolites responsible for the mutagenic activities of 2,4- and 2,6-DNT. (C) 1998 Elsevier Science B.V. Al l rights reserved.