[Molecular pharmacology of polymorphic arylamine N-acetyltransferase involved in the metabolism of arylamine drugs]

Abstract

Polymorphic arylamine N-acetyltransferase in the liver determines the N-acetylation rate of arylamines, which has been implicated in the effects and toxicity of amine- and hydrazine-containing drugs. Recently we have demonstrated that there are four types of gene for polymorphic N-acetyltransferase and that gene 1 gives rise to high N-acetyltransferase activity, while gene 2, 3, and 4 correspond to low N-acetyltransferase activity. Analysis of four genes revealed that the point mutations in genes 2, 3, and 4 result in a loss of a restriction site: a BamHI site for gene 2, a TaqI site for gene 3, and a KpnI site for gene 4. Therefore all four genes can be discriminated by genomic Southern blot analysis and also by PCR amplification of the respective site followed by digestion with an appropriate endonuclease.