title: In vitro reaction of the carcinogen, N-hydroxy-2-naphthylamine, with DNA at the C-8 and N2 atoms of guanine and at the N6 atom of adenine.
abstract: The probable ultimate urinary bladder carcinogen, N-hydroxy-2-naphthylamine (N-HO-2-NA), reacted with nucleic acids and proteins under mildly acidic conditions (pH 5) to form covalently bound derivatives. The extent of reaction was in the order: polyguanylic acid > DNA > or = protein > rRNA > tRNA > polyadenylic acid, polyuridylic acid > polycytidylic acid. At pH 7, appreciable reaction occurred only with protein. Enzymatic hydrolyses of the DNA, which contained 1.5 naphthyl residues/1000 nucleotides, yielded 3 nucleoside-arylamine adducts. From chemical, u.v., n.m.r., and mass spectrometric analyses, the adducts were identified as 1-(deoxyguanosin-N2-yl)-2-naphthylamine, 1-(deoxyadenosin-N6-yl)-2-naphthylamine, and a purine ring-opened derivative of N-(deoxyguanosin-8-yl)-2-naphthylamine, tentatively identified as 1-[5-(2,6-diamino-4-oxopyrimidinyl-N6-deoxyriboside)]-3-(2-naphthyl)urea. The properties of these adducts and their possible role in the initiation of carcinogenesis are discussed.
authors.affiliation: National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR 72079, USA.
authors.forename: F F
authors.initials: FF
authors.lastname: Kadlubar
authors.forename: L E
authors.initials: LE
authors.lastname: Unruh
authors.forename: F A
authors.initials: FA
authors.lastname: Beland
authors.forename: K M
authors.initials: KM
authors.lastname: Straub
authors.forename: F E
authors.initials: FE
authors.lastname: Evans
mesh_terms: D015081:2-Naphthylamine / Q000031:analogs & derivatives* / Q000378:metabolism; D000225:Adenine / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D002273:Carcinogens / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D018736:DNA Adducts / Q000737:chemistry* / Q000378:metabolism; D006147:Guanine / Q000737:chemistry* / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D008099:Liver / Q000166:cytology / Q000187:drug effects*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D051381:Rats; D013056:Spectrophotometry, Ultraviolet
chemical_list: D002273:Carcinogens; D018736:DNA Adducts; D006147:Guanine; D004247:DNA; C427203:calf thymus DNA; D015081:2-Naphthylamine; D000225:Adenine; C019424:N-hydroxy-2-naphthylamine