ACS Publications. Most Trusted. Most Cited. Most Read
Screening for DNA Alkylation Mono and Cross-Linked Adducts with a Comprehensive LC-MS3 Adductomic Approach

OR SEARCH CITATIONS

My Activity
Publications

Figure 1Loading Img
Download Hi-Res ImageDownload to MS-PowerPointCite This:Anal. Chem. 2015, 87, 23, 11706-11713
    Article

    Screening for DNA Alkylation Mono and Cross-Linked Adducts with a Comprehensive LC-MS3 Adductomic Approach
    Click to copy article linkArticle link copied!

    View Author Information
    † Department of Health Sciences and Technology, ETH Zurich, Schmelzbergstrasse 9, 8092 Zurich, Switzerland
    ‡ Masonic Cancer Center, University of Minnesota, 2231 Sixth Street SE, Minneapolis, Minnesota 55455, United States
    *E-mail: [email protected]. Fax: (612) 624-3869. Tel.: (612) 624-4240.
    Other Access OptionsSupporting Information (1)

    Analytical Chemistry

    Cite this: Anal. Chem. 2015, 87, 23, 11706–11713
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acs.analchem.5b02759
    Published October 28, 2015
    Copyright © 2015 American Chemical Society
    Request reuse permissions

    Abstract

    Click to copy section linkSection link copied!
    Abstract Image

    A high-resolution/accurate-mass DNA adductomic approach was developed to investigate anticipated and unknown DNA adducts induced by DNA alkylating agents in biological samples. Two new features were added to a previously developed approach to significantly broaden its scope, versatility, and selectivity. First, the neutral loss of a base (guanine, adenine, thymine, or cytosine) was added to the original methodology’s neutral loss of the 2′-deoxyribose moiety to allow for the detection of all DNA base adducts. Second, targeted detection of anticipated DNA adducts based on the reactivity of the DNA alkylating agent was demonstrated by inclusion of an ion mass list for data dependent triggering of MS2 fragmentation events and subsequent MS3 fragmentation. Additionally, untargeted screening of the samples, based on triggering of an MS2 fragmentation event for the most intense ions of the full scan, was included for detecting unknown DNA adducts. The approach was tested by screening for DNA mono and cross-linked adducts in purified DNA and in DNA extracted from cells treated with PR104A, an experimental DNA alkylating nitrogen mustard prodrug currently under investigation for the treatment of leukemia. The results revealed the ability of this new DNA adductomic approach to detect anticipated and unknown PR104A-induced mono and cross-linked DNA adducts in biological samples. This methodology is expected to be a powerful tool for screening for DNA adducts induced by endogenous or exogenous exposures.

    Copyright © 2015 American Chemical Society

    Subjects

    what are subjects

    Read this article

    To access this article, please review the available access options below.

    Get instant access

    Purchase Access

    Read this article for 48 hours. Check out below using your ACS ID or as a guest.

    Recommended

    Access through Your Institution

    You may have access to this article through your institution.

    Your institution does not have access to this content. Add or change your institution or let them know you’d like them to include access.

    Supporting Information

    Click to copy section linkSection link copied!

    The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.analchem.5b02759.

    • Full details regarding cell culture conditions, in vitro reactions with PR104A, sample preparation, and results of the targeted and untargeted analyses (PDF)

    Terms & Conditions

    Most electronic Supporting Information files are available without a subscription to ACS Web Editions. Such files may be downloaded by article for research use (if there is a public use license linked to the relevant article, that license may permit other uses). Permission may be obtained from ACS for other uses through requests via the RightsLink permission system: http://pubs.acs.org/page/copyright/permissions.html.

    Cited By

    Click to copy section linkSection link copied!

    This article is cited by 49 publications.

    1. Nagarjunachary Ragi, Scott J. Walmsley, Foster C. Jacobs, Thomas A. Rosenquist, Viktoriya S. Sidorenko, Lihua Yao, Laura A. Maertens, Christopher J. Weight, Silvia Balbo, Peter W. Villalta, Robert J. Turesky. Screening DNA Damage in the Rat Kidney and Liver by Untargeted DNA Adductomics. Chemical Research in Toxicology 2024, 37 (2) , 340-360. https://doi.org/10.1021/acs.chemrestox.3c00333
    2. Chiung-Wen Hu, Yuan-Jhe Chang, Wei-Hung Chang, Marcus S. Cooke, Yet-Ran Chen, Mu-Rong Chao. A Novel Adductomics Workflow Incorporating FeatureHunter Software: Rapid Detection of Nucleic Acid Modifications for Studying the Exposome. Environmental Science & Technology 2024, 58 (1) , 75-89. https://doi.org/10.1021/acs.est.3c04674
    3. Kevin J. Murray, Peter W. Villalta, Timothy J. Griffin, Silvia Balbo. Discovery of Modified Metabolites, Secondary Metabolites, and Xenobiotics by Structure-Oriented LC–MS/MS. Chemical Research in Toxicology 2023, 36 (11) , 1666-1682. https://doi.org/10.1021/acs.chemrestox.3c00209
    4. Valeria Guidolin, Foster C. Jacobs, Margaret L. MacMillan, Peter W. Villalta, Silvia Balbo. Liquid Chromatography–Mass Spectrometry Screening of Cyclophosphamide DNA Damage In Vitro and in Patients Undergoing Chemotherapy Treatment. Chemical Research in Toxicology 2023, 36 (8) , 1278-1289. https://doi.org/10.1021/acs.chemrestox.3c00008
    5. Morwena J. Solivio, Alessia Stornetta, Julie Gilissen, Peter W. Villalta, Sofie Deschoemaeker, Arne Heyerick, Ludwig Dubois, Silvia Balbo. In Vivo Identification of Adducts from the New Hypoxia-Activated Prodrug CP-506 Using DNA Adductomics. Chemical Research in Toxicology 2022, 35 (2) , 275-282. https://doi.org/10.1021/acs.chemrestox.1c00329
    6. Kevin J. Murray, Erik S. Carlson, Alessia Stornetta, Emily P. Balskus, Peter W. Villalta, Silvia Balbo. Extension of Diagnostic Fragmentation Filtering for Automated Discovery in DNA Adductomics. Analytical Chemistry 2021, 93 (14) , 5754-5762. https://doi.org/10.1021/acs.analchem.0c04895
    7. Christy Chao, Bevin P. Engelward. Applications of CometChip for Environmental Health Studies. Chemical Research in Toxicology 2020, 33 (7) , 1528-1538. https://doi.org/10.1021/acs.chemrestox.9b00393
    8. Carlos Hernandez-Castillo, John Termini, Sarah Shuck. DNA Adducts as Biomarkers To Predict, Prevent, and Diagnose Disease—Application of Analytical Chemistry to Clinical Investigations. Chemical Research in Toxicology 2020, 33 (2) , 286-307. https://doi.org/10.1021/acs.chemrestox.9b00295
    9. Peter Wick, Pauline Franz, Sabrina Manuela Huber, Cordula Hirsch. Innovative Techniques and Strategies for a Reliable High-Throughput Genotoxicity Assessment. Chemical Research in Toxicology 2020, 33 (2) , 283-285. https://doi.org/10.1021/acs.chemrestox.9b00369
    10. Chiung-Wen Hu, Yuan-Jhe Chang, Marcus S. Cooke, Mu-Rong Chao. DNA Crosslinkomics: A Tool for the Comprehensive Assessment of Interstrand Crosslinks Using High Resolution Mass Spectrometry. Analytical Chemistry 2019, 91 (23) , 15193-15203. https://doi.org/10.1021/acs.analchem.9b04068
    11. Scott J. Walmsley, Jingshu Guo, Jinhua Wang, Peter W. Villalta, Robert J. Turesky. Methods and Challenges for Computational Data Analysis for DNA Adductomics. Chemical Research in Toxicology 2019, 32 (11) , 2156-2168. https://doi.org/10.1021/acs.chemrestox.9b00196
    12. Yuxiang Cui, Pengcheng Wang, Yang Yu, Jun Yuan, Yinsheng Wang. Normalized Retention Time for Targeted Analysis of the DNA Adductome. Analytical Chemistry 2018, 90 (24) , 14111-14115. https://doi.org/10.1021/acs.analchem.8b04660
    13. Yang Yu, Pengcheng Wang, Yuxiang Cui, and Yinsheng Wang . Chemical Analysis of DNA Damage. Analytical Chemistry 2018, 90 (1) , 556-576. https://doi.org/10.1021/acs.analchem.7b04247
    14. Jingshu Guo, Peter W. Villalta, and Robert J. Turesky . Data-Independent Mass Spectrometry Approach for Screening and Identification of DNA Adducts. Analytical Chemistry 2017, 89 (21) , 11728-11736. https://doi.org/10.1021/acs.analchem.7b03208
    15. Alessia Stornetta, Peter W. Villalta, Frederike Gossner, William R. Wilson, Silvia Balbo, and Shana J. Sturla . DNA Adduct Profiles Predict in Vitro Cell Viability after Treatment with the Experimental Anticancer Prodrug PR104A. Chemical Research in Toxicology 2017, 30 (3) , 830-839. https://doi.org/10.1021/acs.chemrestox.6b00412
    16. Alessia Stornetta, Maike Zimmermann, George D. Cimino, Paul T. Henderson, and Shana J. Sturla . DNA Adducts from Anticancer Drugs as Candidate Predictive Markers for Precision Medicine. Chemical Research in Toxicology 2017, 30 (1) , 388-409. https://doi.org/10.1021/acs.chemrestox.6b00380
    17. Junfa Yin, Tian Xu, Ning Zhang, and Hailin Wang . Three-Enzyme Cascade Bioreactor for Rapid Digestion of Genomic DNA into Single Nucleosides. Analytical Chemistry 2016, 88 (15) , 7730-7737. https://doi.org/10.1021/acs.analchem.6b01682
    18. Giorgia La Barbera, Marshal Spenser Shuler, Søren Hammershøj Beck, Per Holger Ibsen, Lars Joachim Lindberg, John Gásdal Karstensen, Lars Ove Dragsted. Development of an untargeted DNA adductomics method by ultra-high performance liquid chromatography coupled to high-resolution mass spectrometry. Talanta 2025, 282 , 126985. https://doi.org/10.1016/j.talanta.2024.126985
    19. Mu-Rong Chao, Yuan-Jhe Chang, Marcus S. Cooke, Chiung-Wen Hu. Multi-adductomics: Advancing mass spectrometry techniques for comprehensive exposome characterization. TrAC Trends in Analytical Chemistry 2024, 180 , 117900. https://doi.org/10.1016/j.trac.2024.117900
    20. Mengqiu Cao, Xinyu Zhang. DNA Adductomics: A Narrative Review of Its Development, Applications, and Future. Biomolecules 2024, 14 (9) , 1173. https://doi.org/10.3390/biom14091173
    21. Zhangjin He, Ziqi Wang, Liping Lu, Xiayan Wang, Guangsheng Guo. Enhanced recognition of G-quadruplex DNA oxidative damage based on DNA-mediated charge transfer. Bioelectrochemistry 2024, 158 , 108714. https://doi.org/10.1016/j.bioelechem.2024.108714
    22. Xiaoqing Li, Hui Zeng, Li Zhang, Jing Zhang, Yinlong Guo, Jiapeng Leng. An integrated LC-MS/MS platform for noninvasive urinary nucleus acid adductomics: A pilot study for tobacco exposure. Journal of Hazardous Materials 2024, 474 , 134780. https://doi.org/10.1016/j.jhazmat.2024.134780
    23. Alessandro Vacchini, Andrew Chancellor, Qinmei Yang, Rodrigo Colombo, Julian Spagnuolo, Giuliano Berloffa, Daniel Joss, Ove Øyås, Chiara Lecchi, Giulia De Simone, Aisha Beshirova, Vladimir Nosi, José Pedro Loureiro, Aurelia Morabito, Corinne De Gregorio, Michael Pfeffer, Verena Schaefer, Gennaro Prota, Alfred Zippelius, Jörg Stelling, Daniel Häussinger, Laura Brunelli, Peter Villalta, Marco Lepore, Enrico Davoli, Silvia Balbo, Lucia Mori, Gennaro De Libero. Nucleobase adducts bind MR1 and stimulate MR1-restricted T cells. Science Immunology 2024, 9 (95) https://doi.org/10.1126/sciimmunol.adn0126
    24. Shugo Suzuki, Min Gi, Masami Komiya, Asuka Obikane, Arpamas Vachiraarunwong, Masaki Fujioka, Anna Kakehashi, Yukari Totsuka, Hideki Wanibuchi. Evaluation of the Mechanisms Involved in the Development of Bladder Toxicity following Exposure to Occupational Bladder Cancer Causative Chemicals Using DNA Adductome Analysis. Biomolecules 2024, 14 (1) , 36. https://doi.org/10.3390/biom14010036
    25. Valeria Guidolin, Yupeng Li, Foster C. Jacobs, Margaret L. MacMillan, Peter W. Villalta, Stephen S. Hecht, Silvia Balbo. Characterization and quantitation of busulfan DNA adducts in the blood of patients receiving busulfan therapy. Molecular Therapy - Oncolytics 2023, 28 , 197-210. https://doi.org/10.1016/j.omto.2023.01.005
    26. Yuxiang Cui, Yinsheng Wang. Mass spectrometry-based DNA adductomics. TrAC Trends in Analytical Chemistry 2022, 157 , 116773. https://doi.org/10.1016/j.trac.2022.116773
    27. Giorgia La Barbera, Katrine Dalmo Nommesen, Catalina Cuparencu, Jan Stanstrup, Lars Ove Dragsted. A Comprehensive Database for DNA Adductomics. Frontiers in Chemistry 2022, 10 https://doi.org/10.3389/fchem.2022.908572
    28. Kristine Walters, Alessia Stornetta, Foster Jacobs, Peter W. Villalta, Maria Razzoli, Marianne Grant, Beshay Zordoky, Alessandro Bartolomucci, Antonella Borgatti, Silvia Balbo. Identification of new candidate biomarkers to support doxorubicin treatments in canine cancer patients. BMC Veterinary Research 2021, 17 (1) https://doi.org/10.1186/s12917-021-03062-x
    29. Yuan-Jhe Chang, Marcus S. Cooke, Yet-Ran Chen, Shun-Fa Yang, Pei-Shan Li, Chiung-Wen Hu, Mu-Rong Chao. Is high resolution a strict requirement for mass spectrometry-based cellular DNA adductomics?. Chemosphere 2021, 274 , 129991. https://doi.org/10.1016/j.chemosphere.2021.129991
    30. Yukari Totsuka, Masatoshi Watanabe, Yingsong Lin. New horizons of DNA adductome for exploring environmental causes of cancer. Cancer Science 2021, 112 (1) , 7-15. https://doi.org/10.1111/cas.14666
    31. Lisa A. Peterson, Silvia Balbo, Naomi Fujioka, Dorothy K. Hatsukami, Stephen S. Hecht, Sharon E. Murphy, Irina Stepanov, Natalia Y. Tretyakova, Robert J. Turesky, Peter W. Villalta. Applying Tobacco, Environmental, and Dietary-Related Biomarkers to Understand Cancer Etiology and Evaluate Prevention Strategies. Cancer Epidemiology, Biomarkers & Prevention 2020, 29 (10) , 1904-1919. https://doi.org/10.1158/1055-9965.EPI-19-1356
    32. Paolo Vineis, Oliver Robinson, Marc Chadeau-Hyam, Abbas Dehghan, Ian Mudway, Sonia Dagnino. What is new in the exposome?. Environment International 2020, 143 , 105887. https://doi.org/10.1016/j.envint.2020.105887
    33. Yukari TOTSUKA, Yuya MAESAKO, Hanako ONO, Momoko NAGAI, Mamoru KATO, Min GI, Hideki WANIBUCHI, Shoji FUKUSHIMA, Kazuhiro SHIIZAKI, Hitoshi NAKAGAMA. Comprehensive analysis of DNA adducts (DNA adductome analysis) in the liver of rats treated with 1,4-dioxane. Proceedings of the Japan Academy, Series B 2020, 96 (5) , 180-187. https://doi.org/10.2183/pjab.96.015
    34. Byeong Hwa Yun, Jingshu Guo, Medjda Bellamri, Robert J. Turesky. DNA adducts: Formation, biological effects, and new biospecimens for mass spectrometric measurements in humans. Mass Spectrometry Reviews 2020, 39 (1-2) , 55-82. https://doi.org/10.1002/mas.21570
    35. Yu Tang, Jin‐Lan Zhang. Recent developments in DNA adduct analysis using liquid chromatography coupled with mass spectrometry. Journal of Separation Science 2020, 43 (1) , 31-55. https://doi.org/10.1002/jssc.201900737
    36. Stephen D. Dertinger, Yukari Totsuka, Jason H. Bielas, Ann T. Doherty, Jos Kleinjans, Masamitsu Honma, Francesco Marchetti, Maik J. Schuler, Veronique Thybaud, Paul White, Carole L. Yauk. High information content assays for genetic toxicology testing: A report of the International Workshops on Genotoxicity Testing (IWGT). Mutation Research/Genetic Toxicology and Environmental Mutagenesis 2019, 847 , 403022. https://doi.org/10.1016/j.mrgentox.2019.02.003
    37. Junfa Yin, Ning Zhang, Hailin Wang. Liquid chromatography- mass spectrometry for analysis of DNA damages induced by environmental exposure. TrAC Trends in Analytical Chemistry 2019, 120 , 115645. https://doi.org/10.1016/j.trac.2019.115645
    38. Andrea Carrà, Valeria Guidolin, Romel P. Dator, Pramod Upadhyaya, Fekadu Kassie, Peter W. Villalta, Silvia Balbo. Targeted High Resolution LC/MS3 Adductomics Method for the Characterization of Endogenous DNA Damage. Frontiers in Chemistry 2019, 7 https://doi.org/10.3389/fchem.2019.00658
    39. Jingshu Guo, Robert J. Turesky. Emerging Technologies in Mass Spectrometry-Based DNA Adductomics. High-Throughput 2019, 8 (2) , 13. https://doi.org/10.3390/ht8020013
    40. Matthew R. Wilson, Yindi Jiang, Peter W. Villalta, Alessia Stornetta, Paul D. Boudreau, Andrea Carrá, Caitlin A. Brennan, Eunyoung Chun, Lizzie Ngo, Leona D. Samson, Bevin P. Engelward, Wendy S. Garrett, Silvia Balbo, Emily P. Balskus. The human gut bacterial genotoxin colibactin alkylates DNA. Science 2019, 363 (6428) https://doi.org/10.1126/science.aar7785
    41. Marcus S. Cooke, Chiung-Wen Hu, Yuan-Jhe Chang, Mu-Rong Chao. Urinary DNA adductomics – A novel approach for exposomics. Environment International 2018, 121 , 1033-1038. https://doi.org/10.1016/j.envint.2018.10.041
    42. Yuan-Jhe Chang, Marcus S. Cooke, Chiung-Wen Hu, Mu-Rong Chao. Novel approach to integrated DNA adductomics for the assessment of in vitro and in vivo environmental exposures. Archives of Toxicology 2018, 92 (8) , 2665-2680. https://doi.org/10.1007/s00204-018-2252-6
    43. Alessia Stornetta, Kai-Cheng Kieren Deng, Sara Danielli, H.D. Sarath Liyanage, Shana J. Sturla, William R. Wilson, Yongchuan Gu. Drug-DNA adducts as biomarkers for metabolic activation of the nitro-aromatic nitrogen mustard prodrug PR-104A. Biochemical Pharmacology 2018, 154 , 64-74. https://doi.org/10.1016/j.bcp.2018.04.004
    44. Kai Hu, Ge Zhao, Junwei Liu, Lizhen Jia, Fuwei Xie, Shusheng Zhang, Huimin Liu, Minying Liu. Simultaneous quantification of three alkylated‑purine adducts in human urine using sulfonic acid poly(glycidyl methacrylate‑divinylbenzene)-based microspheres as sorbent combined with LC-MS/MS. Journal of Chromatography B 2018, 1081-1082 , 15-24. https://doi.org/10.1016/j.jchromb.2018.02.028
    45. Gerhard Scherer. Suitability of biomarkers of biological effects (BOBEs) for assessing the likelihood of reducing the tobacco related disease risk by new and innovative tobacco products: A literature review. Regulatory Toxicology and Pharmacology 2018, 94 , 203-233. https://doi.org/10.1016/j.yrtph.2018.02.002
    46. Alessia Stornetta, Valeria Guidolin, Silvia Balbo. Alcohol-Derived Acetaldehyde Exposure in the Oral Cavity. Cancers 2018, 10 (1) , 20. https://doi.org/10.3390/cancers10010020
    47. Peter Villalta, Silvia Balbo. The Future of DNA Adductomic Analysis. International Journal of Molecular Sciences 2017, 18 (9) , 1870. https://doi.org/10.3390/ijms18091870
    48. Chunhe Yao, Yong-Lai Feng. A nontargeted screening method for covalent DNA adducts and DNA modification selectivity using liquid chromatography-tandem mass spectrometry. Talanta 2016, 159 , 93-102. https://doi.org/10.1016/j.talanta.2016.05.074
    49. Melanie M. Erzinger, Cédric Bovet, Katrin M. Hecht, Sabine Senger, Pascale Winiker, Nadine Sobotzki, Simona Cristea, Niko Beerenwinkel, Jerry W. Shay, Giancarlo Marra, Bernd Wollscheid, Shana J. Sturla, . Sulforaphane Preconditioning Sensitizes Human Colon Cancer Cells towards the Bioreductive Anticancer Prodrug PR-104A. PLOS ONE 2016, 11 (3) , e0150219. https://doi.org/10.1371/journal.pone.0150219
    Download PDF
    Go to Analytical Chemistry
    Get e-Alerts
    Get e-Alerts

    Analytical Chemistry

    Cite this: Anal. Chem. 2015, 87, 23, 11706–11713
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acs.analchem.5b02759
    Published October 28, 2015
    Copyright © 2015 American Chemical Society
    Request reuse permissions

    Article Views

    2013

    Altmetric

    -

    Citations

    49
    Learn about these metrics

    Article Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.

    Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.

    The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated.