Laboratory of Chemical Analysis, Department of Veterinary Public Health and Food Safety, Faculty of Veterinary Medicine, Ghent University , Salisburylaan 133, Merelbeke, B-9820, Belgium.
School of Pharmacy and Biomolecular Sciences, Faculty of Science, Liverpool John Moores University , Liverpool, L3 3AF, United Kingdom.
Anal Chem. 2016 Aug 2;88(15):7436-46. doi: 10.1021/acs.analchem.6b00863. Epub 2016 Jul 14.
Covalent binding of endo- or exogenous chemicals to DNA results in the formation of DNA adducts which are reflective of exposure of the human body to DNA-damaging molecules and their metabolic pathways. The study of DNA adduct types and levels in human tissue therefore offers an interesting tool in several fields of research, including toxicology and cancer epidemiology. Over the years, a range of techniques and methods have been developed to study the formation of endo- and exogenous DNA adducts. However, for the simultaneous detection, identification and quantification of both known and unknown DNA adducts, mass spectrometry (MS) is deemed to be the most promising technique. In this perspective, we focus on the analysis of multiple DNA adducts within a sample with the emphasis on untargeted analysis. The advantageous use of MS methodologies for DNA adductome mapping is discussed comprehensively with relevant field examples. In addition, several aspects of study design, sample pretreatment, and analysis are addressed as these factors significantly affect the reliability of DNA adductomics studies.
内源性或外源性化学物质与 DNA 的共价结合导致 DNA 加合物的形成，这反映了人体暴露于 DNA 损伤分子及其代谢途径的情况。因此，研究人类组织中的 DNA 加合物类型和水平为毒理学和癌症流行病学等多个研究领域提供了一种有趣的工具。多年来，已经开发出一系列技术和方法来研究内源性和外源性 DNA 加合物的形成。然而，为了同时检测、鉴定和定量已知和未知的 DNA 加合物，质谱 (MS) 被认为是最有前途的技术。在这方面，我们专注于对样本中多种 DNA 加合物进行分析，重点是进行非靶向分析。本文全面讨论了 MS 方法在 DNA 加合物组图谱分析中的优势，并提供了相关领域的实例。此外，还讨论了研究设计、样品预处理和分析的几个方面，因为这些因素会显著影响 DNA 加合物组学研究的可靠性。
