Carcinogenic potential of arylamine N-acetyltransferase in Asian populations

Abstract

Arylamine N-acetyltransferase (NAT) is a phase II metabolizing enzyme, which belongs to the transferase family; specifically those acyltransferases which transfer various groups except aminoacyl. NATs are found in both prokaryotes and eukaryotes. They generally perform detoxification reactions; however they sometimes participate in the bioconversion of heterocyclic arylamines into electrophilic nitrenium ions, which are directly implicated in the process of tumor initiation. Several human metabolic enzymes are genetically polymorphic. Polymorphism in the NAT1 and NAT2 genes occurs through single nucleotide polymorphisms in a single exon coding region. The NAT enzymes add an acetyl group from the O to the N group of arylacetohydroxates, which causes the activation of arylamine carcinogens and the subsequent production of N-acetoxy-esters. Additional studies are required to determine the specific role of N- and O-acetylation in carcinogenesis, as at present there is limited literature available and no association has been reported between NAT genotype polymorphisms and cancer development within Asian populations. Keywords: Arylamines, N- and O-acetylation, NAT2 gene, Cancer