Further Activation of Oxidised Metabolites of 1-Nitropyrene

Abstract

Abstract The environmental genotoxin 1-nitropyrene owes most of its mutagenic activity in the Salmonella plate incorporation assay with strain TA98 (approximately 300 rev/nmole) to the arylnitrenium ion derived from the hydoxylamine intermediate formed during nitroreduction. In contrast, the major metabolites of 1-nitropyrene, 1-nitropyren-6-ol and 1-acetamidopyren-6-ol, both require oxidative metabolism by S9 fraction to express their mutagenicity in the Salmonella plate incorporation assay. The activity of 1-nitropyren-6-ol exhibits an S9-concentration dependence that is narrow and peaks at 0.2 mg protein per plate (950 rev/nmole), whereas the mutagenicity of 1-acetamidopyren-6-ol increases with increasing S9 up to 3 mg protein per plate (about 1000 rev/nmole). In incubations catalysed by S9, 1-nitropyren-6-ol forms one major metabolite, identified by 1H-NMR as 1-nitropyren-4,6-diol, and 1-acetamidopyren-6-ol gives rise to multiple unidentified products. This pattern of metabolism is consistent with act...