3,2'-Dimethyl-4-aminobiphenyl-DNA adduct formation in tumor target and nontarget organs of rapid and slow acetylator Syrian hamsters cogenic at the NAT2 locus.
DNA adduct formation is an important step in initiation of the carcinogenic process. 3,2'-Dimethyl-4-aminobiphenyl (DMABP) is a well-documented multiorgan carcinogenic aromatic amine in rodents. In the present study, DMABP-DNA adduct levels were measured in rapid (Bio. 82.73/H-Pat(r)) and slow (Bio. 82.73/H-Pat(s)) acetylator Syrian hamsters congenic at the NAT2 locus following a single injection of 33 or 100 mg/kg body wt DMABP. Two DNA adducts, N-(deoxyguanosin-8-yl)-DMABP and 5-(deoxyguanosin-N2-yl)-DMABP, were identified and quantitated by 32P-postlabeling assay. After injection of 33 mg/kg, DMABP-DNA adducts were detected in urinary bladder at 6, 18, 24, and 48 hr with adduct levels increasing up to 48 hr postinjection. DMABP-DNA adducts were not detected 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 significantly 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 and prostate than in colon and heart of rapid and slow acetylator congenic hamsters, whereas 5-(deoxyguanosin-N2-yl)-DMABP levels were significantly higher in prostate than in colon and heart of rapid and slow acetylator congenic hamsters. DMABP-DNA adduct levels in each tissue examined did not differ significantly between rapid and slow acetylator hamsters following either 33 or 100 mg/kg injection. The tissue-dependent differences in DMABP-DNA adduct levels observed in the Syrian hamster differ from those reported in the rat and are consistent with previous studies that show DMABP induces primarily urinary bladder tumors in the Syrian hamster.
Department of Pharmacology and Toxicology, University of North Dakota School of Medicine and Health Sciences, Grand Forks 58202-9037, USA.
Y
Y
Feng
W
W
Jiang
A C
AC
Deitz
D W
DW
Hein
D000107:Acetylation / Q000187:drug effects; D000611:Aminobiphenyl Compounds / Q000633:toxicity*; D000818:Animals; D001191:Arylamine N-Acetyltransferase / Q000235:genetics* / Q000378:metabolism; D003110:Colonic Neoplasms / Q000139:chemically induced* / Q000235:genetics* / Q000378:metabolism; D006224:Cricetinae; D018736:DNA Adducts / Q000737:chemistry / Q000187:drug effects*; D008647:Mesocricetus; D009928:Organ Specificity / Q000187:drug effects; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced* / Q000235:genetics* / Q000378:metabolism
D000611:Aminobiphenyl Compounds; D018736:DNA Adducts; C001042:2',3-dimethyl-4-aminobiphenyl; D001191:Arylamine N-Acetyltransferase