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 b oth rodent and human carcinogenesis, The colon carcinogen 3,2'-dimethy l-4-aminobiphenyl (DMAB), like other arylamines, undergoes N-acetylati on and O-acetylation by polymorphic acetyltransferase (NAT2), In the p resent 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-NAT2(r) and Bio 1 .5/H-NAT2(s), respectively), differing only at the NAT2 gene locus and other closely linked loci, The animals received DMAB (75 mg/kg body w eight 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 inject ion ACF were observed in the DMAB treated hamsters, but not in the con trols, However, the number of ACF was three times higher (P = 0.016) i n the colons of the NAT2(r) hamsters compared with the colons of the N AT2(s) 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 col on after 10 weeks, but there was no difference between the NAT2(r) and NAT2(s) hamsters, Further scanning electron microscopic and histologi cal examination of ACF observed with the light microscope, revealed th e same gross morphology and therefore confirmed the basis for the scor ing of ACF. The ACF in hamster colons were in principle similar to the lesions observed in other species.