Editorial: Mass Spectrometry for Adductomic Analysis
- 1Oxidative Stress Group, Florida International University, United States
- 2Chung Shan Medical University, Taiwan
exposure. The authors also provide valuable insight into some of the technical challenges that these analyses present.In an exciting potential medical application of protein adductomics, Geib et al. characterize the specific adducts formed when the products of acetaminophen (APAP; paracetamol) interact with key cellular defenses against toxicity (the glutathione S-transferases). APAP-induced hepatotoxicity is the most common cause of acute liver failure in the Western world, making it a major public health problem. Metabolism of APAP generates a reactive intermediate which can react with glutathione and protein thiols. LC-MS/MS analysis revealed seven modified cysteine sites, including two unique sites, demonstrating the power of both untargeted and targeted approaches.The identification of both DNA and protein adducts, discovered during adductomics analysis, is challenging due to the large size of the datasets generated, and the lack of data processing approaches. Whereas proteomics analysis has benefited from technological advances in mass spectrometry, and bioinformatics, this has yet to fully translate to protein (and DNA) adductomics. Nunes et al., inspired by the workflows used in metabolomics, developed a novel analysis approach for the identification of covalently-modified peptides. The strategy was tested by the analysis of histone-derive adducts from HepG2 and THLE2 cells treated with glycidamide, and the results compared against standard methodology. Crucially, the new strategy identified adducts not seen with the conventional approach, and appears likely to advance the protein adductomics field further.Although cellular DNA adductomics is less well established than protein, the field is gaining momentum. In this collection, two reports illustrate the strengths of DNA adductomics, the potential for it to significantly advance our understanding of the links between environmental exposures and disease, and the scope for further methodological and application advances. Carra et al. aimed to develop a screening methodology for all known endogenously generated DNA adducts using high resolution data-dependent scanning, an extensive MS 2 fragmentation inclusion list of all known endogenous adducts, and neutral loss MS 3 triggering to profile all DNA modifications. Crucially, the high sensitivity required to detect some of these low abundance adducts was achieved by decreasing extraneous background signal through pre-and post-DNA hydrolysis steps, and the optimization of several instrument parameters. The success of these improvements was demonstrated in an animal model of lung carcinogenesis. This is a prime example of a concerted approach to refine existing methodology, which can benefit the entire field. Adoption of the lessons learnt from this work should further advance the quality of data, and hence biological significance, achieved by cellular DNA adductomics.In vitro genotoxicity is a first line test when screening new chemical agents, and is generally performed using high throughput assays. However, confirmation of DNA adduct identities can be a time-consuming and expensive process. For the first time, Takeshita and Kanaly describe
Keywords: DNA, protein, adductomics, Adducts, Genomic Instability, Mass spectometry, Exposure, Disease
Received: 25 Sep 2019;
Accepted: 04 Nov 2019.
Copyright: © 2019 Cooke, Hu and Chao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Prof. Marcus S. Cooke, Florida International University, Oxidative Stress Group, Miami, United States, firstname.lastname@example.org
Prof. Chiung-Wen Hu, Chung Shan Medical University, Taichung, 40201, Taiwan, email@example.com
Prof. Mu-Rong Chao, Chung Shan Medical University, Taichung, 40201, Taiwan, firstname.lastname@example.org