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 colorectal cancer has created interest in experimental animal models to study the relationship of N-acetyltransferase phenotype to colon cancer. Colon cytosols from inbred mouse lines were assayed for the ability to N-acetylate 2-aminofluorene to determine if the mouse model of the N-acetyltransferase polymorphism could be used to study this relationship. The results indicate that the colon acetylcoenzyme A: 2-aminofluorene-N-acetyltransferase activity parallels that of the liver. Colon activity from slow acetylator (A and B6.A) mouse lines is significantly lower than that of rapid acetylator (B6, B6.D, and A.B6) lines. p-Aminobenzoic acid N-acetyltransferase activity also differed between colon cytosols from rapid and slow acetylator strains. Isoniazid acetylation in colon and in liver did not differ between phenotypes. Northern blot analysis demonstrated the presence of mRNA for both NAT-1 and NAT-2 in mouse colon as well as in mouse liver. These results indicate that the N-acetyltransferase polymorphism is expressed in mouse colon when 2-aminofluorene or p-aminobenzoic acid is used as substrate and therefore the mouse may be a model for study of the effect of acetylator phenotype on development of colorectal cancer in humans.
Levy
G N
GN
Department of Pharmacology, University of Michigan, Ann Arbor 48109-0626.
Martell
K J
KJ
Weber
W W
WW
D010129:4-Aminobenzoic Acid / Q000378:metabolism; D000107:Acetylation; D000818:Animals; D001191:Arylamine N-Acetyltransferase / Q000235:genetics / Q000378:metabolism*; D015152:Blotting, Northern; D002474:Cell-Free System; D002851:Chromatography, High Pressure Liquid; D003106:Colon / Q000378:metabolism*; D003600:Cytosol / Q000201:enzymology; D005449:Fluorenes / Q000378:metabolism*; D006801:Humans; D007538:Isoniazid / Q000378:metabolism; D008099:Liver / Q000201:enzymology; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D011110:Polymorphism, Genetic; D012313:RNA / Q000235:genetics / Q000378:metabolism
D005449:Fluorenes; C012177:2-aminofluorene; D012313:RNA; D001191:Arylamine N-Acetyltransferase; D010129:4-Aminobenzoic Acid; D007538:Isoniazid