title: 2-Aminofluorene-DNA adduct levels in tumor-target and nontarget organs of rapid and slow acetylator Syrian hamsters congenic at the NAT2 locus.
abstract: DNA adduct formation is an important initial event in chemical carcinogenesis. Metabolic activation and deactivation pathways are involved in aromatic amine carcinogenesis, and genetic polymorphism in the N-acetyltransferase 2 (NAT2) gene is associated with differential susceptibility to cancer from aromatic amine chemicals. In the present study, aromatic amine-DNA adduct levels were measured in rapid (Bio. 82.73/H-Patr) and slow (Bio. 82.73/H-Patr) acetylator Syrian hamsters congenic at the NAT2 locus following a single injection of 2-aminofluorene (60 mg/kg). The major DNA adduct, N-(deoxyguanosin-8-yl)-2-aminofluorene (C8-AF), was detected and quantitated by 32P-postlabeling assay at 6, 18, 24, 36, and 48 hr postinjection. Peak levels of C8-AF were achieved at 18-36 hr post-injection in both rapid and slow acetylators. C8-AF levels were significantly higher in tumor-target organs (liver and urinary bladder) than in nontarget organs (heart, colon, and prostate). Significant differences in C8-AF levels between rapid and slow acetylators in liver, heart, colon, and prostate were not observed. However, C8-AF levels in urinary bladder were significantly (four-fold) higher in rapid versus slow acetylators. These results suggest that 2-aminofluorene forms significantly higher levels of DNA adducts in tumor-target organs than in non-target organs and that acetyltransferase polymorphism plays a significant role in 2-aminofluorene-DNA adduct formation in urinary bladder of Syrian hamster.
authors.affiliation: Department of Pharmacology and Toxicology, University of North Dakota School of Medicine and Health Sciences, Grand Forks 58202-9037, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Feng
authors.forename: W
authors.initials: W
authors.lastname: Jiang
authors.forename: D W
authors.initials: DW
authors.lastname: Hein
mesh_terms: D000107:Acetylation; D000818:Animals; D006224:Cricetinae; D018736:DNA Adducts / Q000096:biosynthesis* / Q000187:drug effects; D005449:Fluorenes / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008647:Mesocricetus; D009153:Mutagens / Q000494:pharmacology*; D001743:Urinary Bladder / Q000187:drug effects* / Q000378:metabolism
chemical_list: D018736:DNA Adducts; D005449:Fluorenes; D009153:Mutagens; C012177:2-aminofluorene