{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T11:22:40Z","timestamp":1784200960675,"version":"3.55.0"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T00:00:00Z","timestamp":1742169600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T00:00:00Z","timestamp":1742169600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100018778","name":"Al-Azhar University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100018778","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Ionizing radiation, from the DNA centric view, elicits biological effects and health consequences solely through energy deposition events in the cell nucleus. At higher radiation doses, this is likely true; however, at low doses, non-targeted effects, a subcategory of which is the adaptive response, tend to dominate. Controversies exist over the definition of low dose. From a radiation therapy view, it is defined as 0.5\u20130.7\u00a0Gy. Therefore, we investigated the effects of exposure to ionizing radiation with or without a 0.5\u00a0Gy priming dose. Techniques including comet assay, flow cytometry, fluorescence microscopy, and real-time quantitative PCR were employed. In normal lung fibroblasts (WI-38), there was a statistically significant difference in mean normalized tail moments when comparing treatment with the challenge dose alone to treatment with a 0.5\u00a0Gy priming dose prior to the challenge dose (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05). Moreover, pretreatment with a 0.5\u00a0Gy priming dose reduced G1 phase cell cycle arrest and cell death\u2014either through apoptosis or mitotic catastrophe\u2014induced by the subsequent 2\u00a0Gy exposure. Similarly, A549 Cells pre-exposed to a 0.5\u00a0Gy priming dose before a 2\u00a0Gy exposure showed a lower percentage of apoptosis than those exposed to the 2\u00a0Gy alone. Mechanistically, cells responded to a priming 0.5\u00a0Gy by increasing the expression of HMOX1, SOD, and Bcl2 while decreasing of IL-1\u03b2 and TNF-\u03b1. In conclusion, 0.5\u00a0Gy induces an adaptive response in lung normal and cancer cell against subsequent high doses of \u03b3-rays. Modulation of the HO-1\/Nrf2 and apoptosis pathways underlie the resistance observed in primed cells.<\/jats:p>","DOI":"10.1038\/s41598-025-91667-9","type":"journal-article","created":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T17:06:29Z","timestamp":1742231189000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["0.5\u00a0Gy confers resistance to a subsequent high dose of \u03b3-rays by modulating HO-1\/Nrf2 and apoptosis pathways"],"prefix":"10.1038","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2842-1360","authenticated-orcid":false,"given":"Yasser F.","family":"Ali","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrahim M.","family":"Hassan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hussein M.","family":"Abdelhafez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2689-7480","authenticated-orcid":false,"given":"Omar S.","family":"Desouky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,17]]},"reference":[{"key":"91667_CR1","unstructured":"UNSCEAR, Sources, Effects Risks of Ionizing Radiation. Report To the General Assembly Scientific Annexes AB. UNSCEAR 2012 Report. United Nations Scientific Committee on the Effects of Atomic Radiation. United Nations Sales Publication E.16.IX.1 (United Nations, 2015)."},{"issue":"2","key":"91667_CR2","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1269\/jrr.07094","volume":"49","author":"M Ito","year":"2008","unstructured":"Ito, M. et al. Effect of low-dose total-body irradiation on transplantability of tumor cells in syngeneic mice. J. Radiat. Res. 49 (2), 197\u2013201 (2008).","journal-title":"J. Radiat. Res."},{"issue":"5","key":"91667_CR3","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1667\/RR0689.1","volume":"166","author":"TK Day","year":"2006","unstructured":"Day, T. K. et al. Extremely low priming doses of X radiation induce an adaptive response for chromosomal inversions in pKZ1 mouse prostate. Radiat. Res. 166 (5), 757\u2013766 (2006).","journal-title":"Radiat. Res."},{"issue":"3","key":"91667_CR4","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1667\/0033-7587(2003)159[0320:LDORIT]2.0.CO;2","volume":"159","author":"RE Mitchel","year":"2003","unstructured":"Mitchel, R. E. et al. Low doses of radiation increase the latency of spontaneous lymphomas and spinal osteosarcomas in cancer-prone, radiation-sensitive Trp53 heterozygous mice. Radiat. Res. 159 (3), 320\u2013327 (2003).","journal-title":"Radiat. Res."},{"issue":"3","key":"91667_CR5","first-page":"180","volume":"13","author":"SL Gong","year":"2000","unstructured":"Gong, S. L. et al. Adaptive response of thymocyte apoptosis and cell cycle progression induced by low dose X-ray irradiation in mice. Biomed. Environ. Sci. 13 (3), 180\u2013188 (2000).","journal-title":"Biomed. Environ. Sci."},{"issue":"3","key":"91667_CR6","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1007\/s004110050073","volume":"36","author":"WF Heidenreich","year":"1997","unstructured":"Heidenreich, W. F., Paretzke, H. G. & Jacob, P. No evidence for increased tumor rates below 200 mSv in the atomic bomb survivors data. Radiat. Environ. Biophys. 36 (3), 205\u2013207 (1997).","journal-title":"Radiat. Environ. Biophys."},{"key":"91667_CR7","unstructured":"Fry, R. J. M. A Note On The Dose-Rate-Effectiveness Factor and Its (2013). https:\/\/three.jsc.nasa.gov\/articles\/DDREF.pdf"},{"issue":"1","key":"91667_CR8","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1186\/s13014-015-0471-z","volume":"10","author":"M Niewald","year":"2015","unstructured":"Niewald, M. et al. Randomized multicenter follow-up trial on the effect of radiotherapy on painful heel spur (plantar fasciitis) comparing two fractionation schedules with uniform total dose: first results after three months\u2019 follow-up. Radiat. Oncol. 10 (1), 174 (2015).","journal-title":"Radiat. Oncol."},{"issue":"1","key":"91667_CR9","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1080\/09553008914551231","volume":"56","author":"JD Shadley","year":"1989","unstructured":"Shadley, J. D. & Wiencke, J. K. Induction of the adaptive response by X-rays is dependent on radiation intensity. Int. J. Radiat. Biol. 56 (1), 107\u2013118 (1989).","journal-title":"Int. J. Radiat. Biol."},{"issue":"2","key":"91667_CR10","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1667\/0033-7587(2002)158[0181:DRFATL]2.0.CO;2","volume":"158","author":"EJ Broome","year":"2002","unstructured":"Broome, E. J., Brown, D. L. & Mitchel, R. E. Dose responses for adaption to low doses of (60)Co gamma rays and (3)H beta particles in normal human fibroblasts. Radiat. Res. 158 (2), 181\u2013186 (2002).","journal-title":"Radiat. Res."},{"issue":"3","key":"91667_CR11","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1097\/HP.0000000000001649","volume":"124","author":"SM Hussien","year":"2023","unstructured":"Hussien, S. M. Radio-adaptive response induced by Low-dose ionizing radiation in innate immunity for radiotherapy. Health Phys. 124 (3), 166\u2013174 (2023).","journal-title":"Health Phys."},{"issue":"2","key":"91667_CR12","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1023\/A:1007525531145","volume":"15","author":"SH Park","year":"1999","unstructured":"Park, S. H. et al. Different induction of adaptive response to ionizing radiation in normal and neoplastic cells. Cell. Biol. Toxicol. 15 (2), 111\u2013119 (1999).","journal-title":"Cell. Biol. Toxicol."},{"issue":"3","key":"91667_CR13","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1269\/jrr.07072","volume":"49","author":"H Jiang","year":"2008","unstructured":"Jiang, H. et al. Low-dose radiation induces adaptive response in normal cells, but not in tumor cells: in vitro and in vivo studies. J. Radiat. Res. 49 (3), 219\u2013230 (2008).","journal-title":"J. Radiat. Res."},{"issue":"4","key":"91667_CR14","first-page":"356","volume":"17","author":"H Yu","year":"2013","unstructured":"Yu, H. et al. Different responses of tumor and normal cells to low-dose radiation. Contemp. Oncol. (Pozn). 17 (4), 356\u2013362 (2013).","journal-title":"Contemp. Oncol. (Pozn)"},{"key":"91667_CR15","doi-asserted-by":"crossref","unstructured":"Kobayashi, D. et al. One-step protocol for evaluation of the mode of radiation-induced clonogenic cell death by fluorescence microscopy. J. Vis. Exp., 128 (2017).","DOI":"10.3791\/56338"},{"issue":"3","key":"91667_CR16","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1093\/mutage\/gel014","volume":"21","author":"R Genghini","year":"2006","unstructured":"Genghini, R. et al. Determination of genotoxicity of classical swine fever vaccine in vitro by cytogenetic and comet tests. Mutagenesis 21 (3), 213\u2013217 (2006).","journal-title":"Mutagenesis"},{"key":"91667_CR17","doi-asserted-by":"crossref","unstructured":"Poss, K. D. & Tonegawa, S. Reduced stress defense in heme oxygenase 1-deficient cells. Proc. Natl. Acad. Sci.. 94(20), 10925\u201310930 (1997).","DOI":"10.1073\/pnas.94.20.10925"},{"issue":"16","key":"91667_CR18","doi-asserted-by":"publisher","first-page":"5804","DOI":"10.3390\/ijms21165804","volume":"21","author":"J Nuszkiewicz","year":"2020","unstructured":"Nuszkiewicz, J., Wo\u017aniak, A. & Szewczyk-Golec, K. Ionizing radiation as a source of oxidative Stress\u2014The protective role of melatonin and vitamin D. Int. J. Mol. Sci. 21 (16), 5804 (2020).","journal-title":"Int. J. Mol. Sci."},{"issue":"7","key":"91667_CR19","doi-asserted-by":"publisher","first-page":"6662","DOI":"10.3390\/ijms24076662","volume":"24","author":"D Yang","year":"2023","unstructured":"Yang, D. et al. Pharmacological targeting of Bcl-2 induces caspase 3-Mediated cleavage of HDAC6 and regulates the autophagy process in colorectal Cancer. Int. J. Mol. Sci. 24 (7), 6662 (2023).","journal-title":"Int. J. Mol. Sci."},{"issue":"1","key":"91667_CR20","doi-asserted-by":"publisher","first-page":"e762","DOI":"10.1002\/iid3.762","volume":"11","author":"P Wang","year":"2023","unstructured":"Wang, P. et al. Role of signal transduction pathways in IL-1\u03b2-induced apoptosis: pathological and therapeutic aspects. Immun. Inflamm. Dis. 11 (1), e762 (2023).","journal-title":"Immun. Inflamm. Dis."},{"issue":"3\u20134","key":"91667_CR21","doi-asserted-by":"publisher","first-page":"482","DOI":"10.1089\/ars.2005.7.482","volume":"7","author":"M Shakibaei","year":"2005","unstructured":"Shakibaei, M. et al. Redox regulation of apoptosis by members of the TNF superfamily. Antioxid. Redox Signal. 7 (3\u20134), 482\u2013496 (2005).","journal-title":"Antioxid. Redox Signal."},{"issue":"2","key":"91667_CR22","doi-asserted-by":"publisher","first-page":"155932582412458","DOI":"10.1177\/15593258241245804","volume":"22","author":"X Wei","year":"2024","unstructured":"Wei, X. et al. Enhancement of the tumor suppression effect of High-dose radiation by Low-dose Pre-radiation through Inhibition of DNA damage repair and increased pyroptosis. Dose-Response 22 (2), 15593258241245804 (2024).","journal-title":"Dose-Response"},{"key":"91667_CR23","doi-asserted-by":"crossref","unstructured":"Yang, G. et al. Distinct biological effects of low-dose radiation on normal and cancerous human lung cells are mediated by ATM signaling. Oncotarget 7(44). (2016).","DOI":"10.18632\/oncotarget.12379"},{"issue":"4","key":"91667_CR24","doi-asserted-by":"publisher","first-page":"155932582110399","DOI":"10.1177\/15593258211039931","volume":"19","author":"XC Wang","year":"2021","unstructured":"Wang, X. C. et al. The adaptive responses in Non-Small cell lung Cancer A549 cell lines induced by Low-Dose ionizing radiation and the variations of MiRNA expression. Dose Response. 19 (4), 15593258211039931 (2021).","journal-title":"Dose Response"},{"issue":"1","key":"91667_CR25","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.mrfmmm.2011.07.002","volume":"715","author":"B Dieriks","year":"2011","unstructured":"Dieriks, B. et al. Repeated exposure of human fibroblasts to ionizing radiation reveals an adaptive response that is not mediated by interleukin-6 or TGF-\u03b2. Mutat. Research\/Fundamental Mol. Mech. Mutagen. 715 (1), 19\u201324 (2011).","journal-title":"Mutat. Research\/Fundamental Mol. Mech. Mutagen."},{"issue":"3","key":"91667_CR26","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1667\/RR0561.1","volume":"166","author":"K Otsuka","year":"2006","unstructured":"Otsuka, K. et al. Activation of antioxidative enzymes induced by Low-Dose-Rate Whole-Body \u03b3 irradiation: adaptive response in terms of initial DNA damage. Radiat. Res. 166 (3), 474\u2013478 (2006).","journal-title":"Radiat. Res."},{"issue":"1","key":"91667_CR27","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1093\/jrr\/rrs077","volume":"54","author":"B Wang","year":"2012","unstructured":"Wang, B. et al. Relieved residual damage in the hematopoietic system of mice rescued by radiation-induced adaptive response (Yonezawa Effect). J. Radiat. Res. 54 (1), 45\u201351 (2012).","journal-title":"J. Radiat. Res."},{"issue":"1","key":"91667_CR28","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1007\/s11010-012-1227-9","volume":"364","author":"D Saini","year":"2012","unstructured":"Saini, D. et al. Transcription profile of DNA damage response genes at G0 lymphocytes exposed to gamma radiation. Mol. Cell. Biochem. 364 (1), 271\u2013281 (2012).","journal-title":"Mol. Cell. Biochem."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-91667-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-91667-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-91667-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T17:06:35Z","timestamp":1742231195000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-91667-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,17]]},"references-count":28,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["91667"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-91667-9","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,17]]},"assertion":[{"value":"11 December 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 February 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 March 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"9199"}}