Van den Driessche Bart, Van Dongen Walter, Lemière Filip, Esmans Eddy L
Department of Chemistry, Nucleoside Research and Mass Spectrometry Unit, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp, Belgium.
Rapid Commun Mass Spectrom. 2004;18(17):2001-7. doi: 10.1002/rcm.1578.
The study of defects in DNA caused by xenobiotics, more particularly the study of DNA adducts, is an important field in cancer aetiology. The analysis of low abundance DNA adducts formed in vivo both in animals and humans requires the development and implementation of highly sensitive analytical methods. Since only a minute amount of DNA can be isolated (ca. 100 microg) it is evident that the amount of sample consumed per analysis should be as small as possible in order to gather as much analytical information as possible. In this article an example is given of how this problem can be solved by the implementation of data-dependent acquisitions using capillary liquid chromatography coupled to electrospray tandem mass spectrometry. As a case study the alkylation of DNA by melphalan is presented. Slight modifications of the chromatographic conditions (mobile and stationary phases) can allow the automated analysis of other kinds of DNA adducts.
对外源化学物质引起的DNA缺陷的研究，尤其是对DNA加合物的研究，是癌症病因学中的一个重要领域。分析在动物和人类体内形成的低丰度DNA加合物需要开发和应用高灵敏度的分析方法。由于只能分离出微量的DNA（约100微克），显然每次分析所消耗的样品量应尽可能少，以便获取尽可能多的分析信息。本文给出了一个例子，说明如何通过采用毛细管液相色谱-电喷雾串联质谱联用的数据依赖型采集方法来解决这个问题。作为一个案例研究，展示了美法仑对DNA的烷基化作用。对色谱条件（流动相和固定相）进行轻微调整，就可以实现对其他种类DNA加合物的自动化分析。
