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Gut. Mar 1998; 42(3): 402–409.
PMCID: PMC1727045

Expression of arylamine N-acetyltransferase in human intestine


Background—Arylamine N-acetyltransferases in humans (NAT1 and NAT2) catalyse the acetylation of arylamines including food derived heterocyclic arylamine carcinogens. Other substrates include the sulphonamide 5-aminosalicylic acid (5-ASA), which is an NAT1 specific substrate; N-acetylation of 5-ASA is a major route of metabolism. NAT1 and NAT2 are both polymorphic.
Aims—To investigate NAT expression in apparently healthy human intestines in order to understand the possible role of NAT in colorectal cancer and in the therapeutic response to 5-ASA.
Methods—The intestines of four organ donors were divided into eight sections. DNA was prepared for genotyping NAT1 and NAT2 and enzymic activities of NAT1 and NAT2 were determined in cytosols prepared from each section. Tissue was fixed for immunohistochemistry with specific NAT antibodies. Western blotting was carried out on all samples of cytosol and on homogenates of separated muscle and villi after microdissection.
Results—NAT1 activity of all cytosols was greater than NAT2 activity. NAT1 and NAT2 activities correlated with the genotypes of NAT1 and NAT2 and with the levels of NAT1 staining determined by western blotting. The ratio of NAT1:NAT2 activities showed interindividual variations from 2 to 70. NAT1 antigenic activity was greater in villi than in muscle. NAT1 was detected along the length of the villi in the small intestine. In colon samples there was less NAT1 at the base of the crypts with intense staining at the tips.
Conclusions—The interindividual variation in NAT1 and NAT2 in the colon could affect how individuals respond to exposure to specific NAT substrates including carcinogens and 5-ASA.

Keywords: arylamine N-acetyltransferase; 5-aminosalicylate; colorectal cancer; drug metabolism; inflammatory bowel disease; diet

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Selected References

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Figures and Tables

Figure 1
Identification of NAT1 alleles by PCR and restriction enzyme digestion with Bsa0I. Template DNA was amplified with the primer pair N539 (sense) and N714 (antisense) and then digested with Bsa0I. The wild type allele (G at position 560 of coding sequence) ...
Figure 2
Detection of NAT enzymic activity in different sections along the length of human intestine. (a) Enzymic acivity of NAT1 was determined in cytosols with p-aminobenzoic acid; (b) NAT2 activity was determined with sulphamethazine. (c) Ratios of activities of ...
Figure 3
Expression of NAT1 in human intestine detected by western blotting. (a) Samples of mucosal cytosol along the length of human intestine from individual 22/3 were prepared and analysed by polyacrylamide gel electrophoresis and western blotting (tracks 2 ...
Figure 4
Expression of NAT in human intestine detected by immunohistochemistry with antiserum 177. Sections of duodenum (a,c) and colon (b,d) were stained with antiserum 177 (diluted 1 in 3000) (a,b) or the corresponding dilutions of preimmune serum (c,d). Intestine ...
Figure 5
Expression of NAT1 in human intestine detected by immunohistochemistry with antiserum 184. Small intestine from individual 22/3 was stained with antiserum 184 (diluted 1/800) (a,c) or with the corresponding dilution of preimmune serum (b,d). Original magnification: ...
Figure 6
Determination of NAT expression in villi and muscle by western blotting. Villi were microdissected from muscle samples of small intestinal samples (corresponding to track 4 of fig 3a) and large intestine (corresponding to track 7 of fig 3a). The mucosa ...

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