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Laboratory of Biochemical Risk Analysis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709 [D. A. B, A. H.]; Division of Molecular Epidemiology, National Center for Toxicological Research, Jefferson, Arkansas 72079 [A. F. B. F. F. K.]; University of Arkansas Medical Sciences, Arkansas Cancer Research Center, Little Rock, Arkansas 72205 [N. P. L.]; and Department of Pharmacology, University of Western Australia, Perth, Australia 6009 [K. F. I.]
Exposures to carcinogens present in the diet, in cigarette smoke, or in the environment have been associated with increased risk of bladder and colorectal cancer. The aromatic amines and their metabolites, a class of carcinogen implicated in these exposures, and be N- or O-acetylated by the NAT1 and NAT2 enzymes. Acetylation may result in activation to DNA-reactive metabolites or, in some cases, detoxification. Many studies have focused on genetic variation in NAT2 and its potential as a risk factor in bladder and colorectal cancer; however, NAT1 activity is higher in bladder and colonic mucosa than NAT2, and the NAT1 enzyme also exhibits phenotypic variation among human tissue samples. We hypothesized that specific genetic variants in the polyadenylation signal of the NAT1 gene would alter tissue levels of NAT1 enzyme activity and used a PCR-based method to distinguish polymorphic NAT1 alleles in samples obtained from 45 individuals. When the NAT1 genotype was compared with the NAT1 phenotype in bladder and colon tissue samples (p-aminobenzoic acid activity), we observed a 
2-fold higher NAT1 enzyme activity in samples from individuals who inherited a variant polyadenylation signal (NAT1*10 allele). This is the first observation relating a genetic polymorphism in NAT1 to a rapid/slow NAT1 phenotype in humans.
1 To whom correspondence should be addressed at C3-03, NIEHS, P.O. Box 12233, Research Triangle Park, NC 27709.
2 A. H., Visiting Fellow, National Institute of Environmental Health Sciences, was supported by a National Institute of Environmental Health Sciences Intramural Research Award to D. A. B. and had partial support from the Finnish Academy of Sciences, the Finnish Cancer Society, and the Finnish Work Environmental Fund.
Received 7/12/95. Accepted 10/ 5/95.
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