title: Identification of N2-(deoxyguanosin-8-yl)-2-amino-3,8-dimethyl-imidazo[4,5- f]quinoxaline 3',5'-diphosphate, a major DNA adduct, detected by nuclease P1 modification of the 32P-postlabeling method, in the liver of rats fed MeIQx.
abstract: The carcinogenic heterocyclic amine 2-amino-3,8-dimethyl-imidazo[4,5-f]quinoxaline (MeIQx) is widely distributed in cooked foods. The nuclease P1 method increased the sensitivity of the standard 32P-postlabeling analysis about 1000-fold for detection of MeIQx-DNA adducts. The recovery of MeIQx-DNA adducts by the nuclease P1 method was determined to be about 50% using liver DNA of a rat treated with [14C]MeIQx intragastrically. By the nuclease P1 method five adducts were detected in the liver DNA of rats fed MeIQx and two of them, including the most abundant one, were identified as MeIQx-deoxyguanosine adducts by comparison with the adducts formed in in vitro reactions of N-acetoxy-2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline with the four 2'-deoxyribonucleotides. The most abundant adduct in vivo was identified as N2-(deoxyguanosin-8-yl)-MeIQx 3',5'-diphosphate (3',5'-pdGp-C8-MeIQx). MeIQx-DNA adduct levels in human tissues could be determined by the nuclease P1 modification of the 32P-postlabeling method in combination with HPLC, and thus provide information on the roles of MeIQx in human carcinogenesis.
authors.affiliation: Carcinogenesis Division, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Ochiai
authors.forename: H
authors.initials: H
authors.lastname: Nagaoka
authors.forename: K
authors.initials: K
authors.lastname: Wakabayashi
authors.forename: Y
authors.initials: Y
authors.lastname: Tanaka
authors.forename: S B
authors.initials: SB
authors.lastname: Kim
authors.forename: A
authors.initials: A
authors.lastname: Tada
authors.forename: H
authors.initials: H
authors.lastname: Nukaya
authors.forename: T
authors.initials: T
authors.lastname: Sugimura
authors.forename: M
authors.initials: M
authors.lastname: Nagao
mesh_terms: D000818:Animals; D002855:Chromatography, Thin Layer; D004247:DNA / Q000032:analysis*; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives / Q000032:analysis; D007553:Isotope Labeling / Q000379:methods*; D008099:Liver / Q000737:chemistry*; D008297:Male; D010761:Phosphorus Radioisotopes; D011810:Quinoxalines / Q000008:administration & dosage / Q000032:analysis*; D051381:Rats; D011916:Rats, Inbred F344; D012680:Sensitivity and Specificity; D015719:Single-Strand Specific DNA and RNA Endonucleases
chemical_list: D010761:Phosphorus Radioisotopes; D011810:Quinoxalines; D006153:Guanosine Diphosphate; C083913:N(2)-(deoxyguanosin-8-yl)-2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline 3',5'-diphosphate; C036990:2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline; D004247:DNA; D015719:Single-Strand Specific DNA and RNA Endonucleases