The Metabolism of 1,8-Dinitropyrene by Salmonella typhimurium

Abstract

S. typhimurium strain TA98/1,8-DNP₆ is resistant to mutagenesis by 1,8-dinitropyrene and is deficient in an acetyl-CoA dependent acetyltransferase activity. Strains TA98 and TA98NR which are acetyltransferase competent are sensitive to 1,8-dinitropyrene mutagenesis. The coincidence of acetyltransferase deficiency and 1,8-dinitropyrene resistance in strain TA98/1,8-DNP₆ implicates acetylation as an important process in the metabolic activation of 1,8-dinitropyrene to a mutagenic intermediate. The acetyltransferase activity can be assayed by observing the formation of 1-N-acetylamino-8-aminopyrene and 1,8-N,N'-diacetyldiaminopyrene from 1,8-diaminopyrene. Reduction of the nitro-function is also an important enzymatic step involved in the activation of 1,8-dinitropyrene. Evidence is presented which suggests that a nitroreductase-acetyltransferase enzyme complex may exist. Further investigations of nitroreductase activity have yielded results which indicate that three distinct nitroreductases exist, one specific for 1,8-dinitropyrene, one specific for 1-nitropyrene and one specific for nitrofurazone. The implications of these findings are discussed and an explanatory model is proposed.