FORMATION OF THE ADDUCT 6-(DEOXYGUANOSIN-N-2-YL)-3-AMINO-BENZO[A]PYRENE FROM THE MUTAGENIC ENVIRONMENTAL CONTAMINANT 3-NITROBENZO[A]PYRENE

3-Nitrobenzo[a]pyrene (3-nitro-B[a]P) is a potent bacterial mutagen as a result of nitroreduction. Reaction of N-hydroxy-3-amino-B[a]P, prep ared in situ from reduction of 3-nitro-B[a]P with calf thymus DNA, was studied. After enzymatic digestion of the DNA, the resulting modified nucleosides were analyzed by thermospray HPLC - MS and high-resolutio n proton NMR spectroscopy. The major adduct was identified as 6-(deoxy guanosin-N2-yl)-3-amino-B[a]P. The same adduct was obtained from incub ation of DNA with 3-nitro-B[a]P in the presence of the mammalian nitro reductase xanthine oxidase, and hypoxanthine. These data indicate that a mammalian nitroreductase can metabolize 3-nitro-B[a]P to an activat ed derivative that reacts with DNA to give a novel adduct distant from the site of N-hydroxylation.