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

• Published in: Mutation research Vol. 420; no. 1; pp. 27 - 32
• Main Authors: Sayama, Michio, Mori, Masa-aki, Shoji, Miki, Uda, Shin-ichi, Kakikawa, Makiko, Kondo, Takashi, Kodaira, Ken-Ichi
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 03.12.1998; Elsevier
• Subjects: Acetyltransferases - chemistry; Azoxy compound; Biological and medical sciences; Carcinogens - metabolism; Carcinogens - toxicity; Chemical mutagenesis; Dinitrobenzenes - metabolism; Dinitrobenzenes - toxicity; Dinitrotoluene; Medical sciences; Mutagenicity; Mutagenicity Tests; Nitroreductase; Nitroreductases - chemistry; O-acetyltransferase; Oxidation-Reduction; Salmonella typhimurium; Salmonella typhimurium - drug effects; Salmonella typhimurium - enzymology; Salmonella typhimurium - genetics; Salmonella typhimurium YG strain; Toxicology; 2-nitroso-4-nitrotoluene, 82414-02-6; 2,4-DNT, 2,4-dinitrotoluene; 2,2′-DM-5,5′-DNAOB, 2,2′-dimethyl-5,5′-dinitroazoxybenzene; Salmonella typhimurium YG strain; 4-nitroso-2-nitrotoluene, 82414-03-7; 2NO4NT, 2-nitroso-4-nitrotoluene; 2A4NT, 2-amino-4-nitrotoluene; 2,6-DNT, 2,6-dinitrotoluene; 4,4′-dimethyl-3,3′-dinitroazoxybenzene, 5679-89-0; 4A2NT, 4-amino-2-nitrotoluene; 4,4′-DM-3,3′-DNAOB, 4,4′-dimethyl-3,3′-dinitroazoxybenzene; NR, nitroreductase; 2-hydroxylamino-6-nitrotoluene, 5805-95-8; 4-amino-2-nitrotoluene, 119-32-4; 2HA6NT, 2-hydroxylamino-6-nitrotoluene; 2,4-dinitrotoluene, 121-14-2; Nitroreductase; 2-amino-4-nitrotoluene, 99-55-8; 4NO2NT, 4-nitroso-2-nitrotoluene; 2,6-dinitrotoluene, 606-20-2; 2A6NT, 2-amino-6-nitrotoluene; 4-hydroxylamino-2-nitrotoluene, 43192-03-6; 2-hydroxylamino-4-nitrotoluene, 95860-07-4; 2-amino-6-nitrotoluene, 603-83-8; Azoxy compound; Dinitrotoluene; O-acetyltransferase; 4HA2NT, 4-hydroxylamino-2-nitrotoluene; Dimethyl sulfoxide, 67-68-5; 2,2′-dimethyl-5,5′-dinitroazoxybenzene, 67151-57-9; 2,2′-DM-3,3′-DNAOB, 2,2′-dimethyl-3,3′-dinitroazoxybenzene; 2-nitroso-6-nitrotoluene, 143922-95-6; Mutagenicity; 2HA4NT, 2-hydroxylamino-4-nitrotoluene; OAT, O-acetyltransferase; 2,2′-dimethyl-3,3′-dinitroazoxybenzene, 5806-00-8; 2NO6NT, 2-nitroso-6-nitrotoluene; Acyltransferases; Enzyme; Metabolite; Mutagenicity testing; Toxicity; Transferases; N-Hydroxyarylamine O-acetyltransferase; Salmonella typhimurium; Enzymatic activity; Ames test; Nitrate reductase; Bacteria; Oxidoreductases; Mutation; Enterobacteriaceae
• ISSN: 1383-5718; 0027-5107; 1879-3592
• DOI: 10.1016/S1383-5718(98)00139-9

Mutagenicities of 2,4- and 2,6-dinitrotoluene (2,4-and 2,6-DNT), and reduced metabolites formed by the incubation of 2,4- and 2,6-DNT with Salmonella typhimurium TA98, were tested using S. typhimurium YG strains possessing high 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 YG1041 and YG1042 were aminonitrotoluenes (2A4NT, 4A2NT)<2,4-DNT<2,2′-dimethyl-5,5′-dinitroazoxybenzene (2,2′-DM-5,5′-DNAOB)≒4-hydroxylamino-2-nitrotoluene (4HA2NT)≪4,4′-dimethyl-3,3′-dinitroazoxybenzene (4,4′-DM-3,3′-DNAOB), and aminonitrotoluenes (2A4NT, 4A2NT)<2,4-DNT<4HA2NT≒4,4′-dimethyl-3,3′-dinitroazoxybenzene (4,4′-DM-3,3′-DNAOB)<2HA4NT, respectively. In addition, the relative mutagenic activities of 2,6-DNT and its related compounds toward YG1041 and YG1042 were 2,6-DNT<2-hydroxylamino-6-nitrotoluene (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 aminohydroxylamino dimethylazoxybenzenes or aminohydroxylamino dimethylazobenzenes produced either by the reduction of hydroxylaminonitrotoluenes or by the reduction of dimethyl dinitroazoxybenzenes are active metabolites responsible for the mutagenic activities of 2,4- and 2,6-DNT.