Acetylation as an Indicator of Risk
Nicholas P. Lang
John L. McClellan VA Hospital and the University of Arkansas for Medical Sciences, Little Rock, Arkansas
Abstract
Aromatic amine acetylation has been recognized for many years as an important metabolic polymorphism in humans because of its relationship to disease. This system serves as a model in risk assessment because of its role in drug and carcinogen activation and detoxification and because of the ease with which it is measured. However, possible interactions of NAT1-NAT2 phenotypes or genotypes illustrate the complexity of xenobiotic metabolism pathways. Moreover, the use of such information for risk assessment is further complicated by the association of the rapid phenotype with increased risk in colon cancer and the slow phenotype with increased risk in urinary bladder cancer. Before this biomarker can be effectively utilized as a significant predictor of individual risk, it will be necessary to identify specific sources of aromatic amine exposure and to characterize further the substrate specificity of NAT1 and NAT2 in relation to the multiplicity of enzyme variants occurring in human populations. -- Environ Health Perspect 105(Suppl 4):763-766 (1997)
Key words: acetylation, phenotyping, NAT1, NAT2, biomarker, risk assessment
This paper was prepared as background for the Workshop on Susceptibility to Environmental Hazards convened by the Scientific Group on Methodologies for the Safety Evaluation of Chemicals (SGOMSEC) held 17-22 March 1996 in Espoo, Finland. Manuscript received at EHP 5 November 1996; accepted 18 November 1996.
Address correspondence to Dr. N.P. Lang, 112/LR, 4300 West 7th Street, Little Rock, AR 72205. Telephone: (501) 660-2038. Fax: (501) 671-2523. E-mail: nplang@life.uams.edu
Abbreviations used: AAMU, 5-acetylamino-6-amino-3-methyluracil; AFMU, 5-acetylamino-6-formylamino-3-methyluracil; CYP1A2, cytochrome P-450 1A2; HPLC, high pressure liquid chromatography; NAT1, N-acetyltransferase 1; NAT2, N-acetyltransferase 2; PABA, p-aminobenzoic acid, SMZ, sulfamethazine; 1X, 1-methyl xanthene.
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Last Update: June 13, 1997