The Future of DNA Adductomic Analysis

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, ³²P-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.