{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T10:06:40Z","timestamp":1789639600379,"version":"4.0.0"},"reference-count":28,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010814","name":"Provincial Natural Science Research Project of Anhui Colleges","doi-asserted-by":"publisher","award":["2025AHGXZK40014"],"award-info":[{"award-number":["2025AHGXZK40014"]}],"id":[{"id":"10.13039\/501100010814","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["11805228"],"award-info":[{"award-number":["11805228"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["11805228"],"award-info":[{"award-number":["11805228"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Low-dose ionizing radiation is known to alter the biological properties of tumor cells. Although clinical computed tomography delivers low-dose radiation, the long-term radiobiological impacts of repeated low-dose X-ray exposure on the malignant progression of lung adenocarcinoma remain poorly defined and require further preclinical clarification. In this preclinical study, we established long-term passaged A549 lung adenocarcinoma cell models subjected to single and fractionated low-dose X-ray irradiation. In vitro functional phenotypes and molecular alterations were further evaluated using murine subcutaneous xenograft and tail vein pulmonary colonization models to assess tumor growth and lung colonization capacity. Long-term low-dose irradiation significantly promoted lung cancer cell proliferation and migration in vitro and enhanced tumor growth and pulmonary colonization in mice. The results for cells cultured in vitro showed that low-dose radiation induced persistent DNA damage responses, modulated p53 expression, and upregulated the expression of epithelial\u2013mesenchymal transition (EMT)- and glycolysis-related proteins, thereby remodeling the aggressive malignant phenotype of lung adenocarcinoma cells. Prolonged low-dose X-ray exposure drives progressive malignant phenotypic remodeling in A549 cells. Our work provides experimental radiobiological evidence of radiation-promoted tumor progression. Importantly, these preclinical findings are restricted to cell culture and animal models and cannot be directly extrapolated to clinical situations.<\/jats:p>","DOI":"10.3390\/ijms27188272","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T09:59:03Z","timestamp":1789639143000},"page":"8272","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Impact of Low-Dose X-Ray Radiation Exposure on Lung Cancer Progression"],"prefix":"10.3390","volume":"27","author":[{"given":"Zhijie","family":"Chen","sequence":"first","affiliation":[{"name":"Teaching and Research Section of Nuclear Medicine, School of Basic Medicine, Anhui Medical University, Hefei 230032, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Xinxin","family":"Guo","sequence":"additional","affiliation":[{"name":"Teaching and Research Section of Nuclear Medicine, School of Basic Medicine, Anhui Medical University, Hefei 230032, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Shijia","family":"Wang","sequence":"additional","affiliation":[{"name":"Teaching and Research Section of Nuclear Medicine, School of Basic Medicine, Anhui Medical University, Hefei 230032, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Peiyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Teaching and Research Section of Nuclear Medicine, School of Basic Medicine, Anhui Medical University, Hefei 230032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ni","family":"Chen","sequence":"additional","affiliation":[{"name":"Teaching and Research Section of Nuclear Medicine, School of Basic Medicine, Anhui Medical University, Hefei 230032, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-8204-2205","authenticated-orcid":false,"given":"Xuanyu","family":"Wang","sequence":"additional","affiliation":[{"name":"Teaching and Research Section of Nuclear Medicine, School of Basic Medicine, Anhui Medical University, Hefei 230032, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,17]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA A Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1001\/jamainternmed.2025.0505","article-title":"Projected Lifetime Cancer Risks From Current Computed Tomography Imaging","volume":"185","author":"Chu","year":"2025","journal-title":"JAMA Intern. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1001\/jama.2021.24287","article-title":"Evaluating the Patient with a Pulmonary Nodule: A Review","volume":"327","author":"Mazzone","year":"2022","journal-title":"JAMA J. Am. Med. Assoc."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1828","DOI":"10.1007\/s00330-019-06523-y","article-title":"Patients undergoing recurrent CT scans: Assessing the magnitude","volume":"30","author":"Rehani","year":"2020","journal-title":"Eur. Radiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"108517","DOI":"10.1016\/j.mrrev.2024.108517","article-title":"Cancer risk associated with low-dose ionizing radiation: A systematic review of epidemiological and biological evidence","volume":"794","author":"Tao","year":"2024","journal-title":"Mutat. Res. Rev. Mutat."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.zemedi.2025.07.002","article-title":"Low-Dose radiation risk in medicine: A look at risk models, challenges, and future prospects","volume":"35","author":"Hoeschen","year":"2025","journal-title":"Z. Med. Phys."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/S1470-2045(22)00655-6","article-title":"Brain cancer after radiation exposure from CT examinations of children and young adults: Results from the EPI-CT cohort study","volume":"24","author":"Hauptmann","year":"2023","journal-title":"Lancet Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Hong, J.Y., Han, K., Jung, J.H., and Kim, J.S. (2019). Association of Exposure to Diagnostic Low-Dose Ionizing Radiation with Risk of Cancer Among Youths in South Korea. Jama Netw. Open, 2.","DOI":"10.1001\/jamanetworkopen.2019.10584"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1093\/jrr\/rrag014","article-title":"Radiation effects of a CT scan on chromosomal aberrations in cancer and non-cancer patients","volume":"67","author":"Kawashima","year":"2026","journal-title":"J. Radiat. 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Cancer"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Lumniczky, K., Impens, N., Armengol, G., Cand\u00e9ias, S., Georgakilas, A.G., Hornhardt, S., Martin, O.A., R\u00f6del, F., and Schaue, D. (2021). Low dose ionizing radiation effects on the immune system. Environ. Int., 149.","DOI":"10.1016\/j.envint.2020.106212"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Chen, J.P., Wang, S., Ding, Y., Xu, D., and Zheng, S.Y. (2025). Radiotherapy-induced alterations in tumor microenvironment: Metabolism and immunity. Front. Cell Dev. Biol., 13.","DOI":"10.3389\/fcell.2025.1568634"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2708","DOI":"10.1158\/1538-7445.AM2025-2708","article-title":"Prediction of radiosensitivity in glioblastoma tumors after standard and low dose rates of ionizing radiation","volume":"85","author":"Rivera","year":"2025","journal-title":"Cancer Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1334","DOI":"10.1038\/s43018-024-00787-0","article-title":"Tumor evolution metrics predict recurrence beyond 10 years in locally advanced prostate cancer","volume":"5","author":"Cresswell","year":"2024","journal-title":"Nat. Cancer"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e20220808","DOI":"10.1084\/jem.20220808","article-title":"Bridging the gap between tumor and disease: Innovating cancer and glioma models","volume":"222","author":"Cirigliano","year":"2024","journal-title":"J. Exp. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"659","DOI":"10.2967\/jnumed.121.262609","article-title":"Signaling Pathways That Drive 18F-FDG Accumulation in Cancer","volume":"63","author":"Salas","year":"2022","journal-title":"J. Nucl. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1016\/j.jacr.2023.02.026","article-title":"The International Commission on Radiological Protection: Working Toward Keeping Recommendations Fit for Purpose","volume":"20","author":"Applegate","year":"2023","journal-title":"J. Am. Coll. Radiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1559325820962615","DOI":"10.1177\/1559325820962615","article-title":"Effects of Low-Dose X-Ray on Cell Growth, Membrane Permeability, DNA Damage and Gene Transfer Efficiency","volume":"18","author":"Wang","year":"2020","journal-title":"Dose-Response"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"5057","DOI":"10.1073\/pnas.0830918100","article-title":"Evidence for a lack of DNA double-strand break repair in human cells exposed to very low x-ray doses","volume":"100","author":"Rothkamm","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1158\/0008-5472.CAN-03-2384","article-title":"A double-strand break repair defect in ATM-deficient cells contributes to radiosensitivity","volume":"64","author":"Riballo","year":"2004","journal-title":"Cancer Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"8984","DOI":"10.1073\/pnas.0501895102","article-title":"formation and repair of DNA double-strand breaks after computed tomography examinations","volume":"102","author":"Rief","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Jakl, L., Markov\u00e1, E., Kol\u00e1rikov\u00e1, L., and Belyaev, I. (2020). Biodosimetry of Low Dose Ionizing Radiation Using DNA Repair Foci in Human Lymphocytes. Genes, 11.","DOI":"10.3390\/genes11010058"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"14205","DOI":"10.1073\/pnas.1002213107","article-title":"Inducible response required for repair of low-dose radiation damage in human fibroblasts","volume":"107","author":"Grudzenski","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2828","DOI":"10.1128\/MCB.01830-08","article-title":"H2AX Is Required for Cell Cycle Arrest via the p53\/p21 Pathway","volume":"29","author":"Fragkos","year":"2009","journal-title":"Mol. Cell Biol."},{"key":"ref_27","first-page":"669","article-title":"DNA double-strand break misrejoining after exposure of primary human fibroblasts to C-K characteristic X rays, 29 kVp X rays and Co-60 gamma rays","volume":"164","author":"Kuhne","year":"2005","journal-title":"Radiat. Res. Off. Organ. Radiat. Res. Soc."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1016\/j.tcb.2020.07.003","article-title":"EMT, MET, Plasticity, and Tumor Metastasis","volume":"30","author":"Bakir","year":"2020","journal-title":"Trends Cell Biol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/18\/8272\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T10:01:39Z","timestamp":1789639299000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/18\/8272"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,17]]},"references-count":28,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["ijms27188272"],"URL":"https:\/\/doi.org\/10.3390\/ijms27188272","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,17]]}}}