Villalta Peter W, Balbo Silvia
Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA.
Division of Environmental Health Sciences, University of Minnesota, Minneapolis, MN 55455, USA.
Int J Mol Sci. 2017 Aug 29;18(9):1870. doi: 10.3390/ijms18091870.
Covalent modification of DNA, resulting in the formation of DNA adducts, plays a central role in chemical carcinogenesis. Investigating these modifications is of fundamental importance in assessing the mutagenicity potential of specific exposures and understanding their mechanisms of action. Methods for assessing the covalent modification of DNA, which is one of the initiating steps for mutagenesis, include immunohistochemistry, P-postlabeling, and mass spectrometry-based techniques. However, a tool to comprehensively characterize the covalent modification of DNA, screening for all DNA adducts and gaining information on their chemical structures, was lacking until the recent development of "DNA adductomics". Advances in the field of mass spectrometry have allowed for the development of this methodology. In this perspective, we discuss the current state of the field, highlight the latest developments, and consider the path forward for DNA adductomics to become a standard method to investigate covalent modification of DNA. We specifically advocate for the need to take full advantage of this new era of mass spectrometry to acquire the highest quality and most reliable data possible, as we believe this is the only way for DNA adductomics to gain its place next to the other "-omics" methodologies as a powerful bioanalytical tool.
DNA的共价修饰会导致DNA加合物的形成，在化学致癌过程中起着核心作用。研究这些修饰对于评估特定暴露的诱变潜力及其作用机制至关重要。评估DNA共价修饰（诱变的起始步骤之一）的方法包括免疫组织化学、P-后标记法和基于质谱的技术。然而，在“DNA加合物组学”最近发展之前，一直缺乏一种能够全面表征DNA共价修饰、筛选所有DNA加合物并获取其化学结构信息的工具。质谱领域的进展使得这种方法得以发展。在这篇综述中，我们讨论了该领域的现状，突出了最新进展，并思考了DNA加合物组学成为研究DNA共价修饰的标准方法的未来发展方向。我们特别主张需要充分利用这个质谱新时代来获取尽可能高质量和最可靠的数据，因为我们相信这是DNA加合物组学能够与其他“组学”方法并列成为强大生物分析工具的唯一途径。
