Application of a high-resolution mass-spectrometry-based DNA adductomics approach for identification of DNA adducts in complex mixtures.

Application of a high-resolution mass-spectrometry-based DNA adductomics approach for identification of DNA adducts in complex mixtures.
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DOI:
10.1021/ac403565m
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发表时间:
2014-02-04
影响因子:
7.4
通讯作者:
Villalta, Peter W.
Villalta, Peter W.
中科院分区:
化学1区
文献类型:
--
作者:
Balbo, Silvia;Hecht, Stephen S.;Upadhyaya, Pramod;Villalta, Peter W.

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液-质联用(LC-MS)是分析DNA共价修饰的首选方法。DNA加合物是这种方法的扩展,允许对已知和未知的DNA加合物进行筛选。在这里报道的研究中,一种新的高分辨率/准确的质量MSN方法已经被开发出来,这对于体内生物样品的研究和评估人类不同暴露所造成的DNA损伤来说是一个重要的进步。该方法是使用18种脱氧核糖核酸加合物的混合物进行测试和优化的,这些加合物代表了所有四种碱基上的一系列生物相关修饰,并使用了暴露于烟草特有的亚硝胺4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone(NNK)的小鼠肝组织的DNA。在第二个实验中,观察到了先前表征的加合物,既有预期的,也有意想不到的。
Liquid chromatography coupled with mass spectrometry (LC-MS) is the method of choice for analysis of covalent modification of DNA. DNA adductomics is an extension of this approach allowing for the screening for both known and unknown DNA adducts. In the research reported here, a new high-resolution/accurate mass MSn methodology has been developed representing an important advance for the investigation of in vivo biological samples and for the assessment of DNA damage from various human exposures. The methodology was tested and optimized using a mixture of 18 DNA adducts representing a range of biologically relevant modifications on all four bases and using DNA from liver tissue of mice exposed to the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). In the latter experiment, previously characterized adducts, both expected and unexpected, were observed.
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发表时间: 2012-08-13
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