Wild C P, Pisani P
Molecular Epidemiology Unit, Research School of Medicine, University of Leeds, United Kingdom.
Cancer Detect Prev. 1998;22(4):273-83. doi: 10.1046/j.1525-1500.1998.cdoa38.x.
Carcinogen DNA and protein adducts promise to provide a more objective measure of human exposure to environmental carcinogens than can be obtained by questionnaire data or environmental measurements. The adducts represent an integration of exposure, absorption, distribution, metabolism, DNA repair, and cell turnover, and thus provide a measure of biologically effective dose; the fact that DNA adducts are involved in the carcinogenic process means such a measure may be more relevant than exposure measures based on ambient levels of a given carcinogen. This approach has been successfully applied to situations where accurate questionnaire data on exposure are difficult to obtain (e.g., for the dietary carcinogens aflatoxins and heterocyclic amines, aromatic amine exposure via environmental tobacco smoke, etc.). Despite the promise of carcinogen DNA and protein adducts, there are a number of issues that must be addressed, including sensitivity, specificity, temporal relationship between exposure and disease, and their mechanistic role in the process of carcinogenesis. This information is a necessary prerequisite to the successful application of these biomarkers into appropriately designed epidemiological studies.
致癌物质DNA和蛋白质加合物有望提供一种比通过问卷调查数据或环境测量更客观的人类接触环境致癌物的衡量标准。这些加合物代表了暴露、吸收、分布、代谢、DNA修复和细胞更新的综合情况,因此提供了一种生物有效剂量的衡量方法;DNA加合物参与致癌过程这一事实意味着这种衡量方法可能比基于特定致癌物环境水平的暴露衡量方法更具相关性。这种方法已成功应用于难以获得准确暴露问卷调查数据的情况(例如,对于膳食致癌物黄曲霉毒素和杂环胺、通过环境烟草烟雾接触芳香胺等)。尽管致癌物质DNA和蛋白质加合物有前景,但仍有许多问题必须解决,包括敏感性、特异性、暴露与疾病之间的时间关系以及它们在致癌过程中的作用机制。这些信息是将这些生物标志物成功应用于精心设计的流行病学研究的必要前提。