Metabolism and biomarkers of heterocyclic aromatic amines in molecular epidemiology studies: lessons learned from aromatic amines.
Metabolism and biomarkers of heterocyclic aromatic amines in molecular epidemiology studies: lessons learned from aromatic amines.
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DOI：
10.1021/tx200135s
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发表时间：
2011-08-15
影响因子：
4.1
通讯作者：
Le Marchand L
中科院分区：
文献类型：
--
作者：
Turesky RJ;Le Marchand L
芳香胺和杂环芳香胺（HAAs）是在烟草燃烧或肉类高温烹饪过程中形成的结构相关的致癌物。这两类致癌物都通过外环胺的n -羟基化进行代谢激活，产生一种常见的中间体——芳基氮离子，这是一种与毒性和DNA损伤有关的关键代谢物。然而，这些化合物的生物化学和化学性质不同，芳香胺和HAAs的不同生物标志物已被开发用于人体生物监测研究。血红蛋白加合物已被广泛用作生物标志物，以监测职业和环境暴露于一些芳香胺；然而，HAAs不形成血红蛋白加合物在可观的水平和其他生物标志物已被寻找。一些流行病学研究调查了饮食中熟肉的摄入量与不同肿瘤部位之间的关系，报告了癌症风险与熟肉摄入量之间的正相关关系，尽管一些研究表明熟肉与癌症风险之间没有关联。大多数流行病学研究的一个主要限制因素是对慢性暴露于HAAs的定量估计的不确定性，因此，在熟肉中形成的HAAs与癌症风险之间的关系很难确定。目前迫切需要建立可用于分子流行病学研究的HAAs的长期生物标志物。在这篇综述文章中，我们强调和比较几种人类长期暴露的典型致癌芳香胺和HAAs的生物化学。研究了主要外源代谢酶的生物化学特性和多态性对这些化学物质生物效应的影响。最后，讨论了已成功应用于芳香胺和HAAs生物监测的分析方法，以及可能在分子流行病学研究中应用的HAAs生物标志物。
Aromatic amines and heterocyclic aromatic amines (HAAs) are structurally related classes of carcinogens that are formed during the combustion of tobacco or during the high-temperature cooking of meats. Both classes of procarcinogens undergo metabolic activation by N-hydroxylation of the exocyclic amine group, to produce a common proposed intermediate, the arylnitrenium ion, which is the critical metabolite implicated in toxicity and DNA damage. However, the biochemistry and chemical properties of these compounds are distinct and different biomarkers of aromatic amines and HAAs have been developed for human biomonitoring studies. Hemoglobin adducts have been extensively used as biomarkers to monitor occupational and environmental exposures to a number of aromatic amines; however, HAAs do not form hemoglobin adducts at appreciable levels and other biomarkers have been sought. A number of epidemiologic studies that have investigated dietary consumption of well-done meat in relation to various tumor sites reported a positive association between cancer risk and well-done meat consumption, although some studies have shown no associations between well-done meat and cancer risk. A major limiting factor in most epidemiological studies is the uncertainty in quantitative estimates of chronic exposure to HAAs and, thus, the association of HAAs formed in cooked meat and cancer risk has been difficult to establish. There is a critical need to establish long-term biomarkers of HAAs that can be implemented in molecular epidemioIogy studies. In this review article, we highlight and contrast the biochemistry of several prototypical carcinogenic aromatic amines and HAAs to which humans are chronically exposed. The biochemical properties and the impact of polymorphisms of the major xenobiotic-metabolizing enzymes on the biological effects of these chemicals are examined. Lastly, the analytical approaches that have been successfully employed to biomonitor aromatic amines and HAAs, and emerging biomarkers of HAAs that may be implemented in molecular epidemiology studies are discussed.
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