2-AMINOFLUORENE-DNA ADDUCT LEVELS IN TUMOR-TARGET AND NONTARGET ORGANS OF RAPID AND SLOW ACETYLATOR SYRIAN-HAMSTERS CONGENIC AT THE NAT2 LOCUS

DNA adduct formation is an important initial event in chemical carcino genesis. Metabolic activation and deactivation pathways are involved i n aromatic amine carcinogenesis, and genetic polymorphism in the N-ace tyltransferase 2 (NAT2) gene is associated with differential susceptib ility to cancer from aromatic amine chemicals. In the present study, a romatic amine-DNA adduct levels were measured in rapid (Bio. 82.73/H-P at(r)) and slow (Bio. 82.73/H-Pat(s)) acetylator Syrian hamsters conge nic at the NAT2 locus following a single injection of 2-aminofluorene (60 mg/kg). The major DNA adduct, N-(deoxyguanosin-8-yl)-2-aminofluore ne (C8-AF), was detected and quantitated by P-32-postlabeling assay at 6, 18, 24, 36, and 48 hr postinjection. Peak levels of C8-AF were ach ieved at 18-36 hr post-injection in both rapid and slow acetylators. C 8-AF levels were significantly higher in tumor-target organs (liver an d urinary bladder) than in nontarget organs (heart, colon, and prostat e). Significant differences in C8-AF levels between rapid and slow ace tylators in liver, heart, colon, and prostate were not observed. Howev er, C8-AF levels in urinary bladder were significantly (four-fold) hig her in rapid versus slow acetylators. These results suggest that 2-ami nofluorene forms significantly higher levels of DNA adducts in tumor-t arget organs than in nontarget organs and that acetyltransferase polym orphism plays a significant role in 2-aminofluorene-DNA adduct formati on in urinary bladder of Syrian hamster. (C) 1996 Academic Press, Inc.