Ma Bin, Stepanov Irina, Hecht Stephen S
Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA.
Toxics. 2019 Mar 19;7(1):16. doi: 10.3390/toxics7010016.
DNA adducts are believed to play a central role in the induction of cancer in cigarette smokers and are proposed as being potential biomarkers of cancer risk. We have summarized research conducted since 2012 on DNA adduct formation in smokers. A variety of DNA adducts derived from various classes of carcinogens, including aromatic amines, polycyclic aromatic hydrocarbons, tobacco-specific nitrosamines, alkylating agents, aldehydes, volatile carcinogens, as well as oxidative damage have been reported. The results are discussed with particular attention to the analytical methods used in those studies. Mass spectrometry-based methods that have higher selectivity and specificity compared to P-postlabeling or immunochemical approaches are preferred. Multiple DNA adducts specific to tobacco constituents have also been characterized for the first time in vitro or detected in vivo since 2012, and descriptions of those adducts are included. We also discuss common issues related to measuring DNA adducts in humans, including the development and validation of analytical methods and prevention of artifact formation.
DNA加合物被认为在吸烟者患癌过程中起核心作用,并被提议作为癌症风险的潜在生物标志物。我们总结了自2012年以来关于吸烟者DNA加合物形成的研究。已报道了多种源自各类致癌物的DNA加合物,包括芳香胺、多环芳烃、烟草特有亚硝胺、烷基化剂、醛类、挥发性致癌物以及氧化损伤。讨论结果时特别关注了这些研究中使用的分析方法。与32P后标记法或免疫化学方法相比,具有更高选择性和特异性的基于质谱的方法更受青睐。自2012年以来,多种烟草成分特有的DNA加合物也首次在体外得到表征或在体内被检测到,文中包含了这些加合物的描述。我们还讨论了与人体DNA加合物测量相关的常见问题,包括分析方法的开发与验证以及伪像形成的预防。