Comparative Formation of DNA Adducts of Nitro-Polycyclic Aromatic Hydrocarbons in Mouse and Rat Liver Microsomes and Cytosols

Abstract We have characterized the DNA adducts of a series of nitro-polycyclic aromatic hydrocarbons (nitro-PAHs) formed under anaerobic conditions in vitro. Although the DNA adducts of nitro-PAHs formed through enzymatic nitroreduction are generally the C8-deoxyguanosyl adducts, nitroreduction of 1-nitrobenzo[a]pyrene (1-nitro-BaP), 3-nitro-BaP, and two derivatives in the presence of calf thymus DNA resulted in the N 2-deoxyguanosyl adducts with the deoxyguanosyl moiety remote from the reaction site. Two DNA adducts of this type were also formed from 1-nitropyrene as minor products. These DNA adducts were formed from anaerobic incubation with rat and mouse liver microsomes and cytosols in the presence of calf thymus DNA. Our results suggest that biological formation of this type of DNA adduct is independent of the enzymatic system, but dependent on the geometric structure and/or electronic features of the nitro-PAH molecules.