Lang N P
John L. McClelian VA Hospital, Little Rock, Arkansas, USA.
Environ Health Perspect. 1997 Jun;105 Suppl 4(Suppl 4):763-6. doi: 10.1289/ehp.97105s4763.
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 case 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.
多年来，芳胺乙酰化一直被认为是人类重要的代谢多态性，因为它与疾病有关。由于该系统在药物和致癌物的激活与解毒过程中发挥作用，且检测方法简便，所以它可作为风险评估的模型。然而，NAT1 - NAT2表型或基因型之间可能存在的相互作用说明了异源生物代谢途径的复杂性。此外，快速表型与结肠癌风险增加以及慢速表型与膀胱癌风险增加之间的关联，使得将此类信息用于风险评估变得更加复杂。在这种生物标志物能够有效地作为个体风险的重要预测指标之前，有必要确定芳胺暴露的具体来源，并进一步明确NAT1和NAT2相对于人群中出现的多种酶变体的底物特异性。
