Oral Cell DNA Adducts as Potential Biomarkers for Lung Cancer Susceptibility in Cigarette Smokers
Oral Cell DNA Adducts as Potential Biomarkers for Lung Cancer Susceptibility in Cigarette Smokers
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DOI：
10.1021/acs.chemrestox.6b00372
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发表时间：
2017-01-01
影响因子：
4.1
通讯作者：
Hecht, Stephen S.
中科院分区：
文献类型：
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作者：
Hecht, Stephen S.
这一观点考虑使用口腔细胞DNA加合物，以及暴露和遗传信息，潜在地识别那些吸烟的人患肺癌的最高风险，以便在造成太大损害之前，在相对较小的年龄就开始采取适当的预防措施。现在已经有了成熟和有效的分析方法来定量测定烟草烟雾、毒物和致癌物的尿液和血清代谢物。这些代谢物提供了暴露的概况，在某些情况下还提供了肺癌风险，但它们不提供导致KRAS和TP53等癌症生长控制基因突变的关键DNA损伤参数的信息。研究表明，由于烟草烟雾的现场效应，吸烟者口腔和肺部的变化之间存在相关性。口腔细胞DNA很容易获得，而不是来自肺部的DNA样本。回顾了口腔细胞DNA和唾液DNA分析特定DNA加合物的研究；一些已鉴定的加合物以前也被移植到吸烟者的肺DNA中。讨论了开发一组口腔细胞DNA加合物的多重挑战，这些加合物可以常规地通过质谱仪进行定量。
This perspective considers the use of oral cell DNA adducts, together with exposure and genetic information, to potentially identify those cigarette smokers at highest risk for lung cancer, so that appropriate preventive measures could be initiated at a relatively young age before too much damage has been done. There are now well established and validated analytical methods for the quantitation of urinary and serum metabolites of tobacco smoke toxicants and carcinogens. These metabolites provide a profile of exposure and in some cases lung cancer risk, but they do not yield information on the critical DNA damage parameter that leads to mutations in cancer growth control genes such as KRAS and TP53. Studies demonstrate a correlation between changes in the oral cavity and lung in cigarette smokers, due to the field effect of tobacco smoke. Oral cell DNA is readily obtained in contrast to DNA samples from the lung. Studies in which oral cell DNA and salivary DNA have been analyzed for specific DNA adducts are reviewed; some of the adducts identified have also been previously repotted in lung DNA from smokers. The multiple challenges of developing a panel of oral cell DNA adducts that could be routinely quantified by mass spectrometry are discussed.