POLYMORPHIC N-ACETYLATION OF 2-AMINOFLUORENE BY CELL-FREE COLON EXTRACTS FROM INBRED MICE

The increased risk of rapid acetylator humans for the development of c olorectal cancer has created interest in experimental animal models to study the relationship of N-acetyltransferase phenotype to colon canc er. Colon cytosols from inbred mouse lines were assayed for the abilit y to N-acetylate 2-aminofluorene to determine if the mouse model of th e N-acetyltransferase polymorphism could be used to study this relatio nship. The results indicate that the colon acetylcoenzyme A: 2-aminofl uorene-N-acetyltransferase activity parallels that of the liver. Colon activity from slow acetylator (A and B6.A) mouse lines is significant ly lower than that of rapid acetylator (B6, B6.D, and A.B6) lines. p-A minobenzoic acid N-acetyltransferase activity also differed between co lon cytosols from rapid and slow acetylator strains. Isoniazid acetyla tion in colon and in liver did not differ between phenotypes. Northern blot analysis demonstrated the presence of mRNA for both NAT-1 and NA T-2 in mouse colon as well as in mouse liver. These results indicate t hat the N-acetyltransferase polymorphism is expressed in mouse colon w hen 2-aminofluorene or p-aminobenzoic acid is used as substrate and th erefore the mouse may be a model for study of the effect of acetylator phenotype on development of colorectal cancer in humans.