Abstract:
:The cellular distribution of AcCoA:arylamine N-acetyltransferase (NAT; EC 2.3.1.5) activities was examined in the rat small intestine to determine if heterogeneous cellular distribution contributes to preferential tumor development in the colonic region after exposure to heterocyclic amines (HAs). A chelation/elution method was used to preferentially isolate villus-tip, mid-villus, and crypt enterocytes. Monomorphic (NAT1) and polymorphic (NAT2) activities were determined using N-acetylprocainamide and N-acetamidobenzoic acid formation, respectively. Sucrase-isomaltase (SI) activity was used to confirm that a villus, mid-villus, and crypt cell gradient had been obtained. Utilizing this marker of villus enrichment, a 4- to 10-fold gradient was achieved. NAT1 and NAT2 activities followed this gradient, with the highest NAT activity occurring in the fraction with the highest SI activity. The ratio of NAT2:NAT1 remained essentially constant along the gradient, indicating a similar pattern of expression for both enzymes. This pattern of cellular distribution for the NATs is similar to that reported for cytochrome P450s. This apparent preferential expression of NAT in the villus cells may result in delivery of bioactivated HAs to the lower regions of the intestines as the villus-tip cells are extruded into the intestinal lumen and enter the fecal stream.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Ware JA,Reilly TP,Svensson CKdoi
10.1016/s0006-2952(97)00659-xsubject
Has Abstractpub_date
1998-05-01 00:00:00pages
1475-9issue
9eissn
0006-2952issn
1873-2968pii
S0006-2952(97)00659-Xjournal_volume
55pub_type
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