The Metabolic Activation and DNA Adducts of Dinitropyrenes

Nitrated polycyclic aromatic hydrocarbons (PAHs) are common environmental contaminants that often contain genotoxic activity. Dinitropyrenes are a class of PAHs that are associated with diesel exhaust. In this study, Dr. Beland and colleagues at the University of Arkansas for Medical Sciences sought to determine what factors contribute to the extreme genotoxicity of dinitropyrenes in bacteria and to establish if the same factors were important for the genotoxicity of dinitropyrenes in mammalian systems. First, the investigators evaluated the ability of a mammalian nitroreductase, xanthine oxidase, to catalyze the reduction of 1,3-, 1-6, and 1-8-dinitropyrenes to DNA-binding derivatives. Next, the ability of mammalian cytosolic and microsomal enzymes to catalyze nitroreduction was explored. Finally, Salmonella typhimurium TA1538 and Chinese hamster ovary cells were incubated with each of the dinitropyrenes and compared with mammalian nitroreductase-catalyzed reactions.