Mutagenicity and genotoxicity of nitroarenes. All nitro-containing chemicals were not created equal

Abstract

The nitrated polycyclic aromatic hydrocarbons constitute a group of chemicals of environmental concern which display a broad spectrum of mutagenic, genotoxic and carcinogenic properties. Some members of the group are the most potent direct-acting bacterial mutagens while others exhibit low levels of potencies which require metabolic activation mixtures. Bacterial mutagenicity is dependent upon reduction of the nitro function. In mammalian cell systems the genetic and genotoxic effects of these nitrated chemicals include the induction of unscheduled DNA synthesis, sister-chromatid exchanges, chromosomal aberrations, gene mutations and cell transformation. The qualitative as well as quantitative expression of these effects is dependent upon the species and tissue of origin as well as culture history of the cell which in turn determine their enzymic capabilities and the conversion of these nitroarenes to ultimate mutagens and genotoxicants. In eukaryotic cells the following bioactivation pathways have been recognized: (a) reduction of the nitro moiety, (b) ring oxidation (the nature of which is influenced by the nitro function) followed by reduction of the nitro group, and (c) ring oxidation without concomitant reduction of the nitro moiety.