Metabolism of 1,8‐dinitropyrene by human, rhesus monkey, and rat intestinal microflora

Dinitropyrenes (DNPs) are highly mutagenic in the Salmonella reversion assay and are tumorigenic in rodents. Bacterial nitroreductases have been implicated in the mutagenic activation of DNPs. In this study, we investigated the metabolism of 1,8‐dinitropyrene (1,8‐DNP) by anaerobic bacterial suspensions derived from human feces, and the intestinal contents of rhesus monkeys and rats. The 1,8‐DNP metabolites were isolated by reversed‐phase high performance liquid chromatography, and identified by comparison of their chromatographic and mass spectral properties with those of authentic compounds. All of the intestinal microflora metabolized 1,8‐DNP to 1‐amino‐8‐nitropyrene and 1,8‐diaminopyrene. The mutagenic activity of samples extracted from incubations of human or rat intestinal microflora cultured with 1,8‐DNP was measured by reversion of Salmonella typhimurium TA98. There was a decrease in the mutagenic activities of the extracts with time of incubation that correlated with increased 1‐amino‐8‐nitropyrene and 1,8‐diaminopyrene formation. The decreased mutagenicity of the 1,8‐DNP metabolites was confirmed by conducting assays with authentic 1‐amino‐8‐nitropyrene and 1,8‐diaminopyrene. Both compounds showed much lower mutagenic activity compared to 1,8‐DNP. The results indicate that intestinal microflora have the ability to metabolize 1,8‐DNP to amine derivatives that are less mutagenic than the parent compound.