Mini-Review: Human N-Acetyltransferase Genetic Polymorphisms in Susceptibility to Aromatic Amine and Alkylaniline Genotoxicity

Arylamine N-acetyltransferases are xenobiotic metabolizing enzymes which play a significant role in the metabolism and detoxification of many drugs and carcinogens. Two N-acetyltransferases have been characterized in humans with similar structure but different substrate affinity. N-acetyltransferase 1 (NAT1) is found in many tissues, whereas N-acetyltransferase 2 (NAT2) is found mostly in the liver and gastrointestinal tract. Both NATs are polymorphic and catalyze both N-acetylation (usually deactivation) and O-acetylation (usually activation) of aromatic amine carcinogens. Previous studies, done in bacteria or animals, have reported that exposure to aromatic amines and alkylanilines leads to DNA damage and mutations. Mammalian models transfected with recombinant human NAT alleles have been constructed to investigate the role of NAT polymorphisms in metabolism or genotoxicity of these carcinogens. This mini-review describes biological plausibility for aromatic amine and alkylaniline carcinogenicity that further supports NAT polymorphisms as important factors for aromatic amine and alkylaniline risk assessments. SIGNIFICANCE STATEMENT: This mini-review describes biological plausibility for aromatic amine and alkylaniline carcinogenicity. N-acetyltransferase polymorphisms are important factors for aromatic amine and alkylaniline risk assessments.