{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T12:58:29Z","timestamp":1761483509623,"version":"build-2065373602"},"reference-count":37,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2021,5,5]],"date-time":"2021-05-05T00:00:00Z","timestamp":1620172800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000048","name":"American Cancer Society","doi-asserted-by":"publisher","award":["RSG\u201012\u2010161\u201001\u2010DMC"],"award-info":[{"award-number":["RSG\u201012\u2010161\u201001\u2010DMC"]}],"id":[{"id":"10.13039\/100000048","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["P42ES017198"],"award-info":[{"award-number":["P42ES017198"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Rapid Comm Mass Spectrometry"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>As a new approach to DNA adductomics, we directly reacted intact, double\u2010stranded (ds)\u2010DNA under warm conditions with an alkylating mass tag followed by analysis by liquid chromatography\/mass spectrometry. This method is based on the tendency of adducted nucleobases to locally disrupt the DNA structure (forming a \u201cDNA bubble\u201d) potentially increasing exposure of their nucleophilic (including active hydrogen) sites for preferential alkylation. Also encouraging this strategy is that the scope of nucleotide excision repair is very broad, and this system primarily recognizes DNA bubbles.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A cationic xylyl (CAX) mass tag with limited nonpolarity was selected to increase the retention of polar adducts in reversed\u2010phase high\u2010performance liquid chromatography (HPLC) for more detectability while maintaining resolution. We thereby detected a diversity of DNA adducts (mostly polar) by the following sequence of steps: (1) react DNA at 45\u00b0C for 2 h under aqueous conditions with CAX\u2010B (has a benzyl bromide functional group to label active hydrogen sites) in the presence of triethylamine; (2) remove residual reagents by precipitating and washing the DNA (a convenient step); (3) digest the DNA enzymatically to nucleotides and remove unlabeled nucleotides by nonpolar solid\u2010phase extraction (also a convenient step); and (4) detect CAX\u2010labeled, adducted nucleotides by LC\/MS\n                      <jats:sup>2<\/jats:sup>\n                      or a matrix\u2010assisted laser desorption\/ionization (MALDI)\u2010MS technique.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Examples of the 42 DNA or RNA adducts detected, or tentatively so based on accurate mass and fragmentation data, are as follows: 8\u2010oxo\u2010dGMP, ethyl\u2010dGMP, hydroxyethyl\u2010dGMP (four isomers, all HPLC\u2010resolved), uracil\u2010glycol, apurinic\/apyrimidinic sites, benzo[\n                      <jats:italic>a<\/jats:italic>\n                      ]pyrene\u2010dGMP, and, for the first time, benzoquinone\u2010hydroxymethyl\u2010dCMP. Importantly, these adducts are detected in a single procedure under a single set of conditions. Sensitivity, however, is only defined in a preliminary way, namely the latter adduct seems to be detected at a level of about 4 adducts in 10\n                      <jats:sup>9<\/jats:sup>\n                      nucleotides (S\/N\u2009~30).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>CAX\u2010Prelabeling is an emerging new technique for DNA adductomics, providing polar DNA adductomics in a practical way for the first time. Further study of the method is encouraged to better characterize and extend its performance, especially in scope and sensitivity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/rcm.9095","type":"journal-article","created":{"date-parts":[[2021,4,6]],"date-time":"2021-04-06T04:54:27Z","timestamp":1617684867000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["DNA Adductomics by mass tag prelabeling"],"prefix":"10.1002","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2962-0495","authenticated-orcid":false,"given":"Poguang","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences Northeastern University  Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisabeth","family":"Roider","sequence":"additional","affiliation":[{"name":"Cutaneous Biology Research Center, Massachusetts General Hospital Harvard Medical School  Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael E.","family":"Coulter","sequence":"additional","affiliation":[{"name":"Center for Integrative Neuroscience, UCSF  San Francisco CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher A.","family":"Walsh","sequence":"additional","affiliation":[{"name":"Division of Genetics and Genomics, Boston Children's Hospital, Center for Life Sciences Harvard Medical School  Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caitlin S.","family":"Kramer","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Chemical Biology Northeastern University  Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Penny J.","family":"Beuning","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Chemical Biology Northeastern University  Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0515-0692","authenticated-orcid":false,"given":"Roger W.","family":"Giese","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Northeastern University  Boston MA 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