Distribution of acetyltransferase activities in the intestines of rapid and slow acetylator rabbits

• Published in: Carcinogenesis (New York) 1991-08, Vol.12 (8), p.1465-1469
• Main Authors: Ilett, K.F., Reeves, P.T., Minchin, R.F., Kinnear, B.F., Watson, H.F., Kadlubar, F.F.
• Format: Article
• Language: English
• Subjects: Acetylation; Acetyltransferases - metabolism; Acyltransferases - metabolism; Analytical, structural and metabolic biochemistry; Animals; Arylamine N-Acetyltransferase - metabolism; Biological and medical sciences; Enzymes and enzyme inhibitors; Fundamental and applied biological sciences. Psychology; Intestines - enzymology; Liver - enzymology; Male; Phenotype; Rabbits; Transferases
• ISSN: 0143-3334; 1460-2180
• DOI: 10.1093/carcin/12.8.1465

Epidemiological studies have shown that there is a significantly greater proportion of the rapid acetylator phenotype in patients th colorectal tumors than in controls; phenotype-related differences in bioactivation of dietary or environmental amines in the intestinal epithelium have been suggested as a mechanism for this effect. In the present study, we have used hepatic and intestinal cytosols to compare N-acetyl-transferase (NAT1 and NAT2), O-acetyl-transferase (OAT) and arylhydroxamic acid N,O-acyltransferase (AHAT) distribution in rapid and slow acetylator rabbits. The ratio (rapid/slow) for p-aminobenzoic acid acetylatlon (a selective substrate for NAT1) was 6 in liver, 1.7–2 in small intestine and 1.3–1.5 in large intestine while the ratio of sulfamethazine acetylation (a selective substrate for NAT2) was 150 in liver, 16–22 in small intestine and 1.8–2.5 in large intestine. The ratios (rapid/slow) for DNA binding of N-hydroxy-3,2′-dimethyl-4-aminobiphenyl and N-hydroxy-4-aminobiphenyl (primarily substrates for OAT) were 82–84 in liver, 13–20 in small intestine and 3.8–5.3 in large intestine and for DNA binding of N-hydroxy-2-acetylamidofluorene (a substrate for ABAT), the ratio was 432 in liver, 32–161 in small intestine and 8.8–13.5 in large intestine. The data show also that NAT1 activity is uniformly distributed along the intestinal tract whereas NAT2 activity is highest in the small intestine. In addition, hepatic and intestinal OAT and AHAT but not NAT1 activities in the rabbit intestine are similarly distributed to activities for NAT2, suggesting that NAT2, OAT and AHAT activities are properties of a single protein in the rapid acetylator phenotype. Moreover, OAT and AHAT activities were much higher in tissues from the rapid than the slow phenotype. The data support the hypothesis that phenotype-dependent metabolic activation of N-OH heterocydlic or aromatic amines to reactive acetoxy metabolites may be involved in the etiology of colorectal cancer.