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Med. Pr. 2000;51(3)

N-acetyltransferase genetic polymorphism and its role in the development of neoplastic disease

Polimorfizm genetyczny n-acetylotransferaz i jego znaczenie w powstawaniu choroby nowotworowej

W. Lutz

Abstract

N-acetyltransferases are the enzymes present in the cells of most mammal species. In human cells, the activity of two N-acetyltransferases, known as NAT1 and NAT2, is expressed. These enzymes are coded by two different genes: NAT1 and NAT2. Gene NAT1 isexpressed in the cells of the majority of tissues and organs, whereas gene NAT2 only in the liver and intestine. Acetylation polymorphism and resultant division into the fast and free acetylators is caused by the occurrence of gene wild allele NAT2 and its mutated forms. A given person shows the fast acetylation phenotype if at least one allele NAT2 is wild. The presence of mutation in both alleles NAT2 is manifested by a free acetylation phenotype. It was indicated that gene NAT1 is also polymorphic, and together with its wild form, the mutated forms are also observed. Genetic polymorphism of NAT1 and NAT2 has serious pharmacological and toxicological consequences. Epidemiological studies show that the free acetylation phenotypes are more susceptible to bladder cancer than the fast ones if they smoke or work under exposure to bicyclic aromatic amines. It has also been evidenced that the fast acetylation phenotypes show enhanced risk of large intestine cancer in conditions of environmental and occupational exposure to heterocyclic amines. It has not as yet been found out whether the acetylation status may be linked with the increased risk of lung cancer.