Expression of monomorphic and polymorphic N-acetyltransferases in human colon.
The metabolism of sulfamethazine (SMZ) and p-aminobenzoic acid (PABA) by N-acetyltransferase (NAT) was measured in human colorectal cytosols from 12 slow and 11 rapid acetylators whose genotype was determined independently by a specific polymerase chain reaction. SMZ metabolism was significantly greater in the rapid than in the slow phenotype (192 +/- 22 versus 94 +/- 11 pmol N-acetylsulfamethazine/min/mg protein), while PABA metabolism was similar in both phenotypes (23.7 +/- 4.4 versus 23.0 +/- 3.9 nmol N-acetyl-p-aminobenzoic acid/min/mg protein). Both monomorphic and polymorphic NAT mRNAs were detected by the polymerase chain reaction in the colorectal mucosa of most samples. The finding that polymorphic NAT is expressed in a phenotype-dependent manner in colorectal mucosa indicates that this tissue has the capacity to participate in local bioactivation of dietary and environmental aryl- or heterocyclic amine carcinogens and may explain, in part, the phenotype-dependent occurrence of colorectal cancer.
Ilett
K F
KF
Department of Pharmacology, University of Western Australia, Nedlands.
Ingram
D M
DM
Carpenter
D S
DS
Teitel
C H
CH
Lang
N P
NP
Kadlubar
F F
FF
Minchin
R F
RF
D010129:4-Aminobenzoic Acid / Q000378:metabolism; D000107:Acetylation; D000123:Acetyltransferases / Q000096:biosynthesis* / Q000235:genetics; D000368:Aged; D001483:Base Sequence; D003106:Colon / Q000201:enzymology* / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000032:analysis; D013418:Sulfamethazine / Q000378:metabolism
D012333:RNA, Messenger; D013418:Sulfamethazine; D000123:Acetyltransferases; D010129:4-Aminobenzoic Acid