Identification of two N2-deoxyguanosinyl DNA adducts upon nitroreduction of the environmental mutagen 1-nitropyrene.
1-Nitropyrene, the most abundant nitro-polycyclic aromatic hydrocarbon in the environment, is a known mammalian and bacterial mutagen and a tumorigen in animals. Early studies on DNA adduct characterization for 1-nitropyrene identified N-(deoxyguanosin-8-yl)-1-aminopyrene as the major product from the modification of calf thymus DNA with N-hydroxy-1-aminopyrene, the activated metabolite from nitroreduction of 1-nitropyrene. In this paper, we report the identification of two N2-deoxyguanosinyl adducts, in addition to N-(deoxyguanosin-8-yl)-1-aminopyrene, formed from the reaction of N-hydroxy-1-aminopyrene, prepared in situ, with calf thymus DNA. These DNA adducts were identified as 6-(deoxyguanosin-N2-yl)-1-aminopyrene and 8-(deoxyguanosin-N2-yl)-1-aminopyrene. The two N2-deoxyguanosinyl adducts were also identified in an ascorbic acid-catalyzed activation of 1-nitrosopyrene and in the mammary gland of female Sprague-Dawley rats administered 1-nitropyrene. The DNA adducts were also formed when 1-nitropyrene was metabolized by xanthine oxidase in the presence of calf thymus DNA, and when 1-nitropyrene was activated by rat liver microsomes and cytosols, as well as from DNA isolated from Salmonella typhimurium suspension cultures incubated with 1-nitropyrene.
Herreno-Saenz
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National Center for Toxicological Research, Jefferson, Arkansas 72079, USA.
Evans
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Beland
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Fu
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D000818:Animals; D001205:Ascorbic Acid / Q000737:chemistry; D002384:Catalysis; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D018736:DNA Adducts; D004269:DNA, Bacterial; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000633:toxicity; D004785:Environmental Pollutants; D004847:Epithelial Cells; D004848:Epithelium / Q000737:chemistry; D005260:Female; D008321:Mammary Glands, Animal / Q000737:chemistry / Q000166:cytology; D008862:Microsomes, Liver / Q000737:chemistry; D009153:Mutagens / Q000737:chemistry*; D009584:Nitrogen / Q000737:chemistry*; D011721:Pyrenes / Q000737:chemistry* / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012486:Salmonella typhimurium / Q000235:genetics; D014969:Xanthine Oxidase / Q000737:chemistry
D018736:DNA Adducts; D004269:DNA, Bacterial; D004785:Environmental Pollutants; D009153:Mutagens; D011721:Pyrenes; C045229:N-(deoxyguanosin-8-yl)-1-aminopyrene; D014969:Xanthine Oxidase; D003849:Deoxyguanosine; D009584:Nitrogen; D001205:Ascorbic Acid; C032668:1-nitropyrene