Effect of acetylator genotype on 3,2'-dimethyl-4-aminobiphenyl induced aberrant crypt foci in the colon of hamsters.
Aberrant crypt foci (ACF) are assumed to be preneoplastic lesions in both rodent and human carcinogenesis. The colon carcinogen 3,2'-dimethyl-4-aminobiphenyl (DMAB), like other arylamines, undergoes N-acetylation and O-acetylation by polymorphic acetyltransferase (NAT2). In the present study we characterized ACF in hamster colon for the first time and compared the ability of DMAB to induce ACF in homozygous rapid and slow acetylator congenic Syrian hamsters (Bio 1.5/H-NAT2r and Bio 1.5/H-NAT2s, respectively), differing only at the NAT2 gene locus and other closely linked loci. The animals received DMAB (75 mg/kg body weight s.c.) or vehicle (PBS/DMSO 1:1) as a control, twice weekly for 2 weeks, then once a week for 4 weeks. Ten weeks after the first injection ACF were observed in the DMAB treated hamsters, but not in the controls. However, the number of ACF was three times higher (P=0.016) in the colons of the NAT2r hamsters compared with the colons of the NAT2s hamsters. In the two congenic hamster lines we also studied the induction of ACF with 1,2-dimethylhydrazine (DMH) treatment, a colon carcinogen not metabolized by NAT2. Hamsters given DMH (25 mg/kg body weight s.c.), once a week for 3 weeks, showed ACF induction in the colon after 10 weeks, but there was no difference between the NAT2r and NAT2s hamsters. Further scanning electron microscopic and histological examination of ACF observed with the light microscope, revealed the same gross morphology and therefore confirmed the basis for the scoring of ACF. The ACF in hamster colons were principle similar to the lesions observed in other species.
Paulsen
J E
JE
Department of Environmental Medicine, National Institute of Public Health, Oslo, Norway.
Steffensen
I L
IL
Namork
E
E
Hein
D W
DW
Alexander
J
J
D000107:Acetylation; D000123:Acetyltransferases / Q000235:genetics* / Q000378:metabolism; D000611:Aminobiphenyl Compounds / Q000378:metabolism* / Q000633:toxicity; D000818:Animals; D002273:Carcinogens / Q000378:metabolism* / Q000633:toxicity; D002712:Chlorides / Q000378:metabolism / Q000633:toxicity; D003106:Colon / Q000187:drug effects / Q000648:ultrastructure; D003110:Colonic Neoplasms / Q000139:chemically induced* / Q000473:pathology; D006224:Cricetinae; D004121:Dimethyl Sulfoxide / Q000378:metabolism / Q000633:toxicity; D005838:Genotype; D008297:Male; D008647:Mesocricetus; D008855:Microscopy, Electron, Scanning; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000473:pathology; D011230:Precancerous Conditions / Q000139:chemically induced* / Q000473:pathology
D000611:Aminobiphenyl Compounds; D002273:Carcinogens; D002712:Chlorides; C001042:2',3-dimethyl-4-aminobiphenyl; D000123:Acetyltransferases; D004121:Dimethyl Sulfoxide