{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T18:53:44Z","timestamp":1782154424660,"version":"3.54.5"},"reference-count":43,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100018684","name":"National Health Commission of the People&apos;s Republic of China","doi-asserted-by":"publisher","award":["2022HYX017"],"award-info":[{"award-number":["2022HYX017"]}],"id":[{"id":"10.13039\/501100018684","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018542","name":"Natural Science Foundation of Sichuan Province","doi-asserted-by":"publisher","award":["2025ZNSFSC0658"],"award-info":[{"award-number":["2025ZNSFSC0658"]}],"id":[{"id":"10.13039\/501100018542","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Computational Biology and Chemistry"],"published-print":{"date-parts":[[2026,10]]},"DOI":"10.1016\/j.compbiolchem.2026.109198","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T15:34:24Z","timestamp":1781537664000},"page":"109198","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"P2","title":["Response of MRC-5 human lung fibroblasts to FLASH and conventional radiotherapy: A study on differential DNA damage and transcriptomic response"],"prefix":"10.1016","volume":"124","author":[{"given":"Yi","family":"Jiang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofeng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chongkai","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangping","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaotian","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenkun","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.compbiolchem.2026.109198_bib1","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1126\/science.1088845","article-title":"Dynamics of DNA double-strand breaks revealed by clustering of damaged chromosome domains","volume":"303","author":"Aten","year":"2004","journal-title":"Science"},{"key":"10.1016\/j.compbiolchem.2026.109198_bib2","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1007\/s13246-023-01266-z","article-title":"The current status of FLASH particle therapy: a systematic review","volume":"46","author":"Atkinson","year":"2023","journal-title":"Phys. Eng. Sci. Med."},{"key":"10.1016\/j.compbiolchem.2026.109198_bib3","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1038\/nsmb.3387","article-title":"Genome-wide mapping of long-range contacts unveils clustering of DNA double-strand breaks at damaged active genes","volume":"24","author":"Aymard","year":"2017","journal-title":"Nat. Struct. Mol. Biol."},{"key":"10.1016\/j.compbiolchem.2026.109198_bib4","doi-asserted-by":"crossref","DOI":"10.3389\/fonc.2022.840783","article-title":"SCLC treatment in the immuno-oncology era: current evidence and unmet needs","volume":"12","author":"Belluomini","year":"2022","journal-title":"Front. Oncol."},{"key":"10.1016\/j.compbiolchem.2026.109198_bib5","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.radonc.2019.06.019","article-title":"Treatment of a first patient with FLASH-radiotherapy","volume":"139","author":"Bourhis","year":"2019","journal-title":"Radiother. Oncol."},{"key":"10.1016\/j.compbiolchem.2026.109198_bib6","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1038\/cr.2010.53","article-title":"New insights into p53 activation","volume":"20","author":"Brooks","year":"2010","journal-title":"Cell. Res."},{"key":"10.1016\/j.compbiolchem.2026.109198_bib7","doi-asserted-by":"crossref","first-page":"3158","DOI":"10.1038\/s41467-020-16926-x","article-title":"DNA double-strand breaks induce H2Ax phosphorylation domains in a contact-dependent manner","volume":"11","author":"Collins","year":"2020","journal-title":"Nat. Commun."},{"key":"10.1016\/j.compbiolchem.2026.109198_bib8","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1038\/nrc3088","article-title":"DNA interstrand crosslink repair and cancer","volume":"11","author":"Deans","year":"2011","journal-title":"Nat. Rev. Cancer"},{"key":"10.1016\/j.compbiolchem.2026.109198_bib9","doi-asserted-by":"crossref","first-page":"5885","DOI":"10.1038\/sj.onc.1206701","article-title":"MAPK pathways in radiation responses","volume":"22","author":"Dent","year":"2003","journal-title":"Oncogene"},{"key":"10.1016\/j.compbiolchem.2026.109198_bib10","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1038\/ncb884","article-title":"DNA damage-induced G2\u2013M checkpoint activation by histone H2AX and 53BP1","volume":"4","author":"Fernandez-Capetillo","year":"2002","journal-title":"Nat. Cell. Biol."},{"key":"10.1016\/j.compbiolchem.2026.109198_bib11","doi-asserted-by":"crossref","first-page":"S5","DOI":"10.1016\/j.jtho.2015.12.007","article-title":"Potential of FLASH irradiation to minimize the incidence of radio-induced damage and fibrosis to normal lung in a mouse model","volume":"11","author":"Fouillade","year":"2016","journal-title":"J. Thorac. Oncol."},{"key":"10.1016\/j.compbiolchem.2026.109198_bib12","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.radonc.2021.11.004","article-title":"First demonstration of the FLASH effect with ultrahigh dose rate high-energy X-rays","volume":"166","author":"Gao","year":"2022","journal-title":"Radiother. Oncol."},{"key":"10.1016\/j.compbiolchem.2026.109198_bib13","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1016\/j.jtho.2020.04.028","article-title":"Lung cancer in People's Republic of China","volume":"15","author":"Gao","year":"2020","journal-title":"J. Thorac. Oncol."},{"key":"10.1016\/j.compbiolchem.2026.109198_bib14","doi-asserted-by":"crossref","DOI":"10.3390\/ijms18091979","article-title":"Genome Instability and \u03b3H2AX","volume":"18","author":"Georgoulis","year":"2017","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.compbiolchem.2026.109198_bib15","first-page":"164","article-title":"Insulin and colon cancer","volume":"6","author":"Giovannucci","year":"1995","journal-title":"Cancer Causes Control."},{"key":"10.1016\/j.compbiolchem.2026.109198_bib16","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1126\/science.1099320","article-title":"The pathophysiology of mitochondrial cell death","volume":"305","author":"Green","year":"2004","journal-title":"Science"},{"key":"10.1016\/j.compbiolchem.2026.109198_bib17","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1126\/science.1201940","article-title":"Mitochondria and the autophagy\u2013inflammation\u2013cell death axis in organismal aging","volume":"333","author":"Green","year":"2011","journal-title":"Science"},{"key":"10.1016\/j.compbiolchem.2026.109198_bib18","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1667\/RADE-21-00181.1","article-title":"Mitochondrial damage response and fate of normal cells exposed to FLASH irradiation with protons","volume":"197","author":"Guo","year":"2022","journal-title":"Radiat. Res."},{"key":"10.1016\/j.compbiolchem.2026.109198_bib19","doi-asserted-by":"crossref","DOI":"10.3389\/fcell.2021.672929","article-title":"Ultra-high dose rate FLASH irradiation induced radio-resistance of normal fibroblast cells can be enhanced by hypoxia and mitochondrial dysfunction resulting from loss of cytochrome C","volume":"9","author":"Han","year":"2021","journal-title":"Front. Cell. Dev. Biol."},{"key":"10.1016\/j.compbiolchem.2026.109198_bib20","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.radonc.2020.04.054","article-title":"Ultra-high dose rate effect on circulating immune cells: a potential mechanism for FLASH effect?","volume":"149","author":"Jin","year":"2020","journal-title":"Radiother. Oncol."},{"key":"10.1016\/j.compbiolchem.2026.109198_bib21","doi-asserted-by":"crossref","first-page":"38709","DOI":"10.1039\/D0RA07999E","article-title":"Significant changes in yields of 7-hydroxy-coumarin-3-carboxylic acid produced under FLASH radiotherapy conditions","volume":"10","author":"Kusumoto","year":"2020","journal-title":"RSC Adv."},{"key":"10.1016\/j.compbiolchem.2026.109198_bib22","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1152\/physrev.00028.2011","article-title":"Mammalian MAPK signal transduction pathways activated by stress and inflammation: a 10-year update","volume":"92","author":"Kyriakis","year":"2012","journal-title":"Physiol. Rev."},{"key":"10.1016\/j.compbiolchem.2026.109198_bib23","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.radonc.2020.06.001","article-title":"A physicochemical model of reaction kinetics supports peroxyl radical recombination as the main determinant of the FLASH effect","volume":"153","author":"Labarbe","year":"2020","journal-title":"Radiother. Oncol."},{"key":"10.1016\/j.compbiolchem.2026.109198_bib24","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1038\/ncb997","article-title":"Colocalization of multiple DNA double-strand breaks at a single Rad52 repair centre","volume":"5","author":"Lisby","year":"2003","journal-title":"Nat. Cell. Biol."},{"key":"10.1016\/j.compbiolchem.2026.109198_bib25","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1007\/s00066-024-02322-7","article-title":"Ampelopsis japonica enhances the effect of radiotherapy in non-small cell lung cancer","volume":"201","author":"Liu","year":"2025","journal-title":"Strahlenther. Onkol."},{"key":"10.1016\/j.compbiolchem.2026.109198_bib26","doi-asserted-by":"crossref","DOI":"10.1016\/j.nantod.2023.102042","article-title":"Radiotherapy-activated tumor immune microenvironment: realizing radiotherapy-immunity combination therapy strategies","volume":"53","author":"Luo","year":"2023","journal-title":"Nano Today"},{"key":"10.1016\/j.compbiolchem.2026.109198_bib27","article-title":"FLASH irradiation regulates IFN-\u03b2 induction by mtDNA via cytochrome c leakage","volume":"2024","author":"Lv","year":"2024","journal-title":"bioRxiv"},{"key":"10.1016\/j.compbiolchem.2026.109198_bib28","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1080\/09553000601170469","article-title":"Kinetics and dose-response of residual 53BP1\/\u03b3-H2AX foci: co-localization, relationship with DSB repair and clonogenic survival","volume":"83","author":"Markov\u00e1","year":"2007","journal-title":"Int. J. Radiat. Biol."},{"key":"10.1016\/j.compbiolchem.2026.109198_bib29","doi-asserted-by":"crossref","first-page":"99","DOI":"10.3390\/genes11010099","article-title":"Clustered DNA double-strand breaks: biological effects and relevance to cancer radiotherapy","volume":"11","author":"Nickoloff","year":"2020","journal-title":"Genes"},{"key":"10.1016\/j.compbiolchem.2026.109198_bib30","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/j.mad.2008.03.003","article-title":"Homologous recombination and maintenance of genome integrity: cancer and aging through the prism of human RecQ helicases","volume":"129","author":"Ouyang","year":"2008","journal-title":"Mech. Ageing Dev."},{"key":"10.1016\/j.compbiolchem.2026.109198_bib31","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1083\/jcb.153.3.613","article-title":"Tumor suppressor P53 binding protein 1 (53bp1) is involved in DNA damage\u2013signaling pathways","volume":"153","author":"Rappold","year":"2001","journal-title":"J. Cell. Biol."},{"key":"10.1016\/j.compbiolchem.2026.109198_bib32","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1038\/s41586-018-0237-5","article-title":"Nuclear ARP2\/3 drives DNA break clustering for homology-directed repair","volume":"559","author":"Schrank","year":"2018","journal-title":"Nature"},{"key":"10.1016\/j.compbiolchem.2026.109198_bib33","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1083\/jcb.151.7.1381","article-title":"P53 binding protein 1 (53bp1) is an early participant in the cellular response to DNA double-strand breaks","volume":"151","author":"Schultz","year":"2000","journal-title":"J. Cell. Biol."},{"key":"10.1016\/j.compbiolchem.2026.109198_bib34","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1007\/s10147-021-02108-2","article-title":"Mapping of global, regional and national incidence, mortality and mortality-to-incidence ratio of lung cancer in 2020 and 2050","volume":"27","author":"Sharma","year":"2022","journal-title":"Int. J. Clin. Oncol."},{"key":"10.1016\/j.compbiolchem.2026.109198_bib35","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2208506119","article-title":"FLASH X-ray spares intestinal crypts from pyroptosis initiated by cGAS-STING activation upon radioimmunotherapy","volume":"119","author":"Shi","year":"2022","journal-title":"Proc. Natl. Acad. Sci."},{"key":"10.1016\/j.compbiolchem.2026.109198_bib36","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1111\/resp.13870","article-title":"Radiotherapy treatment for lung cancer: current status and future directions","volume":"25","author":"Vinod","year":"2020","journal-title":"Respirology"},{"key":"10.1016\/j.compbiolchem.2026.109198_bib37","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1038\/s41571-022-00697-z","article-title":"Towards clinical translation of FLASH radiotherapy","volume":"19","author":"Vozenin","year":"2022","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"10.1016\/j.compbiolchem.2026.109198_bib38","doi-asserted-by":"crossref","DOI":"10.3389\/fcell.2019.00100","article-title":"Mitochondria and inflammation: cell death heats up","volume":"7","author":"Vringer","year":"2019","journal-title":"Front. Cell. Dev. Biol."},{"key":"10.1016\/j.compbiolchem.2026.109198_bib39","doi-asserted-by":"crossref","DOI":"10.1016\/j.lfs.2024.123188","article-title":"Cytological changes in radiation-induced lung injury","volume":"358","author":"Wang","year":"2024","journal-title":"Life Sci."},{"key":"10.1016\/j.compbiolchem.2026.109198_bib40","doi-asserted-by":"crossref","first-page":"19579","DOI":"10.1074\/jbc.C300117200","article-title":"Accumulation of checkpoint protein 53BP1 at DNA breaks involves its binding to phosphorylated histone H2AX*","volume":"278","author":"Ward","year":"2003","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.compbiolchem.2026.109198_bib41","doi-asserted-by":"crossref","first-page":"1974","DOI":"10.1002\/mp.15135","article-title":"FLASH radiotherapy with carbon ion beams","volume":"49","author":"Weber","year":"2022","journal-title":"Med. Phys."},{"key":"10.1016\/j.compbiolchem.2026.109198_bib42","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.1093\/nar\/gku1406","article-title":"53BP1 promotes microhomology-mediated end-joining in G1-phase cells","volume":"43","author":"Xiong","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.compbiolchem.2026.109198_bib43","doi-asserted-by":"crossref","DOI":"10.1080\/2162402X.2020.1797292","article-title":"Mitochondrial control of innate immune signaling by irradiated cancer cells","volume":"9","author":"Yamazaki","year":"2020","journal-title":"OncoImmunology"}],"container-title":["Computational Biology and Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1476927126003257?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1476927126003257?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T18:43:31Z","timestamp":1782153811000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1476927126003257"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":43,"alternative-id":["S1476927126003257"],"URL":"https:\/\/doi.org\/10.1016\/j.compbiolchem.2026.109198","relation":{},"ISSN":["1476-9271"],"issn-type":[{"value":"1476-9271","type":"print"}],"subject":[],"published":{"date-parts":[[2026,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Response of MRC-5 human lung fibroblasts to FLASH and conventional radiotherapy: A study on differential DNA damage and transcriptomic response","name":"articletitle","label":"Article Title"},{"value":"Computational Biology and Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.compbiolchem.2026.109198","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"109198"}}