HUMAN ACETYLATOR GENOTYPE - RELATIONSHIP TO COLORECTAL-CANCER INCIDENCE AND ARYLAMINE N-ACETYLTRANSFERASE EXPRESSION IN COLON CYTOSOL

Polymorphic expression of arylamine N-acetyltransferase (EC 2.3.1.5) m ay be a differential risk factor in metabolic activation of arylamine carcinogens and susceptibility to cancers related to arylamine exposur es. Human epidemiological studies suggest that rapid acetylator phenot ype may be associated with higher incidences of colorectal cancer. We used restriction fragment length polymorphism analysis to determine ac etylator genotypes of 44 subjects with colorectal cancer and 28 non-ca ncer subjects of similar ethnic background (i.e., approximately 25% Bl ack and 75% White). The polymorphic N-acetyltransferase gene (NAT2) wa s amplified by the polymerase chain reaction from DNA templates derive d from human colons of colorectal and non-cancer subjects. No signific ant differences in NA T2 allelic frequencies (i. e., WT, M1, M2, M3 al leles) or in acetylator genotypes were found between the colorectal ca ncer and non-cancer groups. No significant differences in NAT2 allelic frequencies were observed between Whites and Blacks or between males and females. Cytosolic preparations from the human colons were tested for expression of arylamine N-acetyltransferase activity. Although N-a cetyltransferase activity was expressed for each of the arylamines tes ted (i. e., p-aminobenzoic acid, 4-aminobiphenyl, 2-aminofluorene, bet a-naphthylamine), no correlation was observed between acetylator genot ype and expression of human colon arylamine N-acetyltransferase activi ty. Similarly, no correlation was observed between subject age and exp ression of human colon arylamine N-acetyltransferase activity. These r esults suggest that arylamine N-acetyltransferase activity expressed i n human colon is catalyzed predominantly by NAT1, an arylamine N-acety ltransferase that is not regulated by NAT2 acetylator genotype. The ab ility to determine acetylator genotype from DNA derived from human sur gical samples should facilitate further epidemiological studies to ass ess the role of acetylator genotype in various cancers.