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 occurrrence of colorectal cancer.