Kaderlik K R, Kadlubar F F
Office of Research (HFT-100), National Center for Toxicological Research, Jefferson, Arkansas 72079, USA.
Pharmacogenetics. 1995;5 Spec No:S108-17. doi: 10.1097/00008571-199512001-00011.
Metabolic polymorphisms have long been recognized as important determinants of carcinogen susceptibility and recent efforts have shown that interindividual differences in specific cytochromes P450, acetyltransferases, sulfotransferases and glutathione S-transferases are often disproportionately represented in epidemiological studies between cancer cases and controls. Concomitantly, biomonitoring of carcinogen-DNA adducts in human tissues using immunochemical, 32P-postlabelling, fluorescence, and mass spectrometric methods have recently provided direct evidence of human exposure to genotoxic aromatic and heterocyclic amines, polycyclic hydrocarbons, alkylating agents, and endogenous products. However, a combined approach is now needed in order to assess the relevance of these findings to cancer etiology, to identify high-risk individuals, and to provide better health monitoring, earlier diagnosis, and cancer prevention. Using this paradigm, results are presented that implicate specific aromatic amines, heterocyclic amines, and polycyclic aromatic hydrocarbons in the etiology of human urinary bladder, colon, and laryngeal cancers.
代谢多态性长期以来一直被认为是致癌物易感性的重要决定因素，最近的研究表明，特定细胞色素P450、乙酰转移酶、磺基转移酶和谷胱甘肽S - 转移酶的个体差异在癌症病例与对照之间的流行病学研究中往往表现得不成比例。与此同时，使用免疫化学、32P后标记、荧光和质谱方法对人体组织中致癌物 - DNA加合物进行生物监测，最近提供了人体接触遗传毒性芳香胺和杂环胺、多环芳烃、烷基化剂及内源性产物的直接证据。然而，现在需要一种综合方法来评估这些发现与癌症病因的相关性，识别高危个体，并提供更好的健康监测、早期诊断和癌症预防。采用这种模式，本文展示的结果表明特定芳香胺、杂环胺和多环芳烃与人类膀胱癌、结肠癌和喉癌的病因有关。
