Formation of the adduct 6-(deoxyguanosin-N2-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, prepared 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-resolution proton NMR spectroscopy. The major adduct was identified as 6-(deoxyguanosin-N2-yl)-3-amino-B[a]P. The same adduct was obtained from incubation of DNA with 3-nitro-B[a]P in the presence of the mammalian nitroreductase xanthine oxidase, and hypoxanthine. These data indicate that a mammalian nitroreductase can metabolize 3-nitro-B[a]P to an activated derivative that reacts with DNA to give a novel adduct distant from the site of N-hydroxylation.
Herreno-Saenz
D
D
National Center for Toxicological Research, Jefferson, AR 72079.
Evans
F E
FE
Abian
J
J
Fu
P P
PP
D000818:Animals; D001580:Benzopyrenes / Q000032:analysis* / Q000378:metabolism*; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000187:drug effects / Q000378:metabolism*; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000032:analysis; D004785:Environmental Pollutants; D009682:Magnetic Resonance Spectroscopy; D008322:Mammals; D013058:Mass Spectrometry; D009153:Mutagens / Q000378:metabolism*; D009601:Nitroreductases / Q000378:metabolism; D014969:Xanthine Oxidase / Q000378:metabolism
D001580:Benzopyrenes; D004785:Environmental Pollutants; D009153:Mutagens; C081446:6-(deoxyguanosin-N(2)-yl)-3-aminobenzo(a)pyrene; C042055:3-nitrobenzo(a)pyrene; D004247:DNA; D014969:Xanthine Oxidase; D009601:Nitroreductases; D003849:Deoxyguanosine