3,2'-DIMETHYL-4-AMINOBIPHENYL-DNA ADDUCT FORMATION IN TUMOR TARGET AND NONTARGET ORGANS OF RAPID AND SLOW ACETYLATOR SYRIAN-HAMSTERS CONGENIC AT THE NAT2 LOCUS

DNA adduct formation is an important step in initiation of the carcino genic process. 3,2'-Dimethyl-4-aminobiphenyl (DMABP) is a well-documen ted multiorgan carcinogenic aromatic amine in rodents. In the present study, DMABP-DNA adduct levels were measured in rapid (Bio. 82.73/H-Pa t(r)) and slow (Bio. 82.73/H-Pat(s)) acetylator Syrian hamsters congen ic at the NAT2 locus following a single injection of 33 or 100 mg/kg b ody wt DMABP, Two DNA adducts, N-(deoxyguanosin-8-yl)-DMABP and 5-(deo xyguanosin-N-2-yl)-DMABP, were identified and quantitated by P-32-post labeling assay. After injection of 33 mg/kg, DMABP-DNA adducts were de tected in urinary bladder at 6, 18, 24, and 48 hr with adduct levels i ncreasing up to 48 hr postinjection. DMABP-DNA adducts were not detect ed in liver, colon, and heart, After injection of 100 mg/kg, DMABP-DNA adducts were detected in urinary bladder, liver, prostate, colon, and heart at 48 hr postinjection. DMABP-DNA adduct levels were significan tly higher in urinary bladder (primary tumor target organ) than in the other organs of both rapid and slow acetylator congenic hamsters. N-( deoxyguanosin-8-yl)-DMABP levels were significantly higher in liver an d prostate than in colon and heart of rapid and slow acetylator congen ic hamsters, whereas 5-(deoxyguanosin-N-2-yl)-DMABP levels were signif icantly higher in prostate than in colon and heart of rapid and slow a cetylator congenic hamsters. DMABP-DNA adduct levels in each tissue ex amined did not differ significantly between rapid and slow acetylator hamsters following either 33 or 100 mg/kg injection. The tissue-depend ent differences in DMABP-DNA adduct levels observed in the Syrian hams ter differ from those reported in the rat and are consistent with prev ious studies that show DMABP induces primarily urinary bladder tumors in the Syrian hamster. (C) 1996 Academic Press, Inc.