Polymorphism in the N-Acetyltransferase 1(NAT1) polyadenylation signal: association of NAT1*10 allele with higher N-acetylation activity in bladder and colon tissue

摘要: Abstract Exposures to carcinogens present in the diet, cigarette smoke, or environment have been associated with increased risk of bladder and colorectal cancer. The aromatic amines their metabolites, a class carcinogen implicated these exposures, be N- O-acetylated by NAT1 NAT2 enzymes. Acetylation may result activation DNA-reactive metabolites or, some cases, detoxification. Many studies focused on genetic variation its potential as factor cancer; however, activity is higher colonic mucosa than NAT2, enzyme also exhibits phenotypic among human tissue samples. We hypothesized that specific variants polyadenylation signal gene would alter levels used PCR-based method distinguish polymorphic alleles samples obtained from 45 individuals. When genotype was compared phenotype colon (p-aminobenzoic acid activity), we observed ∼2-fold individuals who inherited variant (NAT1*10 allele). This first observation relating polymorphism rapid/slow humans.