D. Herrenosaenz et al., FORMATION OF THE ADDUCT 6-(DEOXYGUANOSIN-N-2-YL)-3-AMINO-BENZO[A]PYRENE FROM THE MUTAGENIC ENVIRONMENTAL CONTAMINANT 3-NITROBENZO[A]PYRENE, Carcinogenesis, 14(5), 1993, pp. 1065-1067
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.