IDENTIFICATION OF 2 N-2-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-y1)-1-aminopyrene as the major product from the modification of calf thymus DNA with N-hydroxy-1-aminopyrene, the activated metabolite from nitroreduction of l-nitropyrene. In this paper, we report the identification of two N-2-deoxyguanosinyl adducts, in addition to N-(deoxyguanosin-8-y1)-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-N-2-yl)-1-aminopyrene and 8-(deoxyguanosin-N-2-yl)-1-aminopyrene. The two N-2-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.