{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T03:17:00Z","timestamp":1788923820188,"version":"build-2803163510"},"reference-count":106,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,12,30]],"date-time":"2024-12-30T00:00:00Z","timestamp":1735516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Classical radiation biology as we understand it clearly identifies genomic DNA as the primary target of ionizing radiation. The evidence appears rock-solid: ionizing radiation typically induces DSBs with a yield of ~30 per cell per Gy, and unrepaired DSBs are a very cytotoxic lesion. We know very well the kinetics of induction and repair of different types of DNA damage in different organisms and cell lines. And yet, higher organisms differ in their radiation sensitivity\u2014humans can be unpredictably radiosensitive during radiotherapy; this can be due to genetic defects (e.g., ataxia telangiectasia (AT), Fanconi anemia, Nijmegen breakage syndrome (NBS), and the xeroderma pigmentosum spectrum, among others) but most often is unexplained. Among other mammals, goats (Capra hircus) appear to be very radiosensitive (LD50 = 2.4 Gy), while Mongolian gerbils (Meriones unguiculatus) are radioresistant and withstand quadruple that dose (LD50 = 10 Gy). Primary radiation lethality in mammals is due most often to hematopoietic insufficiency, which is, in the words of Dr. Theodor Fliedner, one of the pioneers of radiation hematology, \u201ca disturbance in cellular kinetics\u201d. And yet, what makes one cell type, or one particular organism, more sensitive to ionizing radiation? The origins of radiosensitivity go above and beyond the empirical evidence and models of DNA damage and repair\u2014as scientists, we must consider other phenomena: the radiation-induced bystander effect (RIBE), abscopal effects, and, of course, genomic instability and immunomodulation. It seems that radiosensitivity is not entirely determined by the mathematics of DNA damage and repair, and it is conceivable that radiation biology may benefit from an informed enquiry into physiology and organism-level signaling affecting radiation responses. The current article is a review of several key aspects of radiosensitivity beyond DNA damage induction and repair; it presents evidence supporting new potential venues of research for radiation biologists.<\/jats:p>","DOI":"10.3390\/ijms26010257","type":"journal-article","created":{"date-parts":[[2024,12,31]],"date-time":"2024-12-31T10:17:40Z","timestamp":1735640260000},"page":"257","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The Significance of the Response: Beyond the Mechanics of DNA Damage and Repair\u2014Physiological, Genetic, and Systemic Aspects of Radiosensitivity in Higher Organisms"],"prefix":"10.3390","volume":"26","author":[{"given":"Peter V.","family":"Ostoich","sequence":"first","affiliation":[{"name":"Institute of Biodiversity and Ecosystem Research, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,30]]},"reference":[{"key":"ref_1","unstructured":"Hall, E.J. (2006). Radiobiology for the Radiologist, Lippincott Williams & Wilkins."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1084\/jem.83.2.89","article-title":"Studies on the chemical nature of the substance inducing transformation of pneumococcal types: II. Effect of desoxyribonuclease on the biological activity of the transforming substance","volume":"83","author":"McCarty","year":"1946","journal-title":"J. Exp. Med."},{"key":"ref_3","first-page":"983","article-title":"De quelques r\u00e9sultats de la radioth\u00e9rapie et essai de fixation d\u2019une technique rationnelle","volume":"143","author":"Tribondeau","year":"1906","journal-title":"CR Seances Acad. Sci. Radiat. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2","DOI":"10.3109\/09553002.2012.717732","article-title":"The law of Bergoni\u00e9 and Tribondeau: A nice formula for a first approximation","volume":"89","author":"Vogin","year":"2013","journal-title":"Int. J. Radiat. Biol."},{"key":"ref_5","first-page":"202","article-title":"Sterilization rontgenienne totale et definitive, sans radiodermite, des testicules du Belier adulte: Conditions de sa realisation","volume":"70","author":"Regaud","year":"1911","journal-title":"Compt Rend. Soc. Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1259\/0007-1285-62-740-679","article-title":"The linear-quadratic formula and progress in fractionated radiotherapy","volume":"62","author":"Fowler","year":"1989","journal-title":"Br. J. Radiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.semradonc.2008.04.004","article-title":"The linear-quadratic model is an appropriate methodology for determining isoeffective doses at large doses per fraction","volume":"Volume 18","author":"Brenner","year":"2008","journal-title":"Seminars in Radiation Oncology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1084\/jem.103.5.653","article-title":"Action of X-rays on mammalian cells","volume":"103","author":"Puck","year":"1956","journal-title":"J. Exp. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/S0006-3495(76)85690-1","article-title":"Lethal response of HeLa cells to X-irradiation in the latter part of the generation cycle","volume":"16","author":"Griffith","year":"1976","journal-title":"Biophys. J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"425","DOI":"10.2307\/3576409","article-title":"Repair processes in radiation biology","volume":"100","author":"Elkind","year":"1984","journal-title":"Radiat. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"451","DOI":"10.2307\/3572962","article-title":"The relative radiosensitivity of the nucleus and cytoplasm of Chinese hamster fibroblasts","volume":"42","author":"Munro","year":"1970","journal-title":"Radiat. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1667\/RR13855.1","article-title":"Induction and repair of DNA DSB as revealed by H2AX phosphorylation foci in human fibroblasts exposed to low-and high-LET radiation: Relationship with early and delayed reproductive cell death","volume":"183","author":"Antonelli","year":"2015","journal-title":"Radiat. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1080\/09603123.2020.1806212","article-title":"Non-ionizing radiation as possible carcinogen","volume":"32","author":"Gupta","year":"2022","journal-title":"Int. J. Environ. Health Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1101\/sqb.2000.65.127","article-title":"Repair of endogenous DNA damage","volume":"Volume 65","author":"Lindahl","year":"2000","journal-title":"Cold Spring Harbor Symposia on Quantitative Biology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"350608","DOI":"10.4061\/2010\/350608","article-title":"From DNA radiation damage to cell death: Theoretical approaches","volume":"2010","author":"Ballarini","year":"2010","journal-title":"J. Nucleic Acids"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1007\/s00411-015-0601-x","article-title":"Modeling radiation-induced cell death: Role of different levels of DNA damage clustering","volume":"54","author":"Carante","year":"2015","journal-title":"Radiat. Environ. Biophys."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Anglada, T., Terradas, M., Hern\u00e1ndez, L., Genesc\u00e0, A., and Mart\u00edn, M. (2016). Analysis of Residual DSBs in Ataxia-Telangiectasia Lymphoblast Cells Initiating Apoptosis. BioMed Res. Int., 2016.","DOI":"10.1155\/2016\/8279560"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1042\/BJ20080413","article-title":"Repair of ionizing radiation-induced DNA double-strand breaks by non-homologous end-joining","volume":"417","author":"Mahaney","year":"2009","journal-title":"Biochem. J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/s00411-019-00826-w","article-title":"Internal microdosimetry of alpha-emitting radionuclides","volume":"59","author":"Hofmann","year":"2020","journal-title":"Radiat. Environ. Biophys."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Barberet, P., Vianna, F., Karamitros, M., Brun, T., Gordillo, N., Moretto, P., Incerti, S., and Seznec, H. (2012). Monte-Carlo dosimetry on a realistic cell monolayer geometry exposed to alpha particles. Phys. Med. Biol., 57.","DOI":"10.1088\/0031-9155\/57\/8\/2189"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1080\/09553008814552021","article-title":"Soft X-ray dosimetry and RBE for survival of Chinese hamster V79 cells","volume":"54","author":"Hoshi","year":"1988","journal-title":"Int. J. Radiat. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1080\/09553009214551031","article-title":"The relative biological effectiveness of 60Co \u03b3-rays, 55 kVp X-rays, 250 kVp X-rays, and 11 MeV electrons at low doses","volume":"61","author":"Spadinger","year":"1992","journal-title":"Int. J. Radiat. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1083\/jcb.146.5.905","article-title":"Megabase chromatin domains involved in DNA double-strand breaks in vivo","volume":"146","author":"Rogakou","year":"1999","journal-title":"J. Cell Biol."},{"key":"ref_24","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":"ref_25","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_26","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/S0027-5107(98)00095-5","article-title":"Kinetics of the formation of chromosome aberrations in X-irradiated human lymphocytes, using PCC and FISH","volume":"404","author":"Darroudi","year":"1998","journal-title":"Mutat. Res. Fundam. Mol. Mech. Mutagen."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/S0027-5107(98)00021-9","article-title":"137Cesium-induced chromosome aberrations analyzed by fluorescence in situ hybridization: Eight years follow up of the Goiania radiation accident victims","volume":"400","author":"Natarajan","year":"1998","journal-title":"Mutat. Res. Fundam. Mol. Mech. Mutagen."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1080\/09553000600972956","article-title":"Radiation tolerance in the tardigrade Milnesium tardigradum","volume":"82","author":"Horikawa","year":"2006","journal-title":"Int. J. Radiat. Biol."},{"key":"ref_29","unstructured":"Bond, V.P., and Robertson, J.S. (1963). Comparison of the Mortality Response of Different Mammalian Species to X-rays and Fast Neutrons, Brookhaven National Lab."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1038\/35054579","article-title":"Normal human mammary epithelial cells spontaneously escape senescence and acquire genomic changes","volume":"409","author":"Romanov","year":"2001","journal-title":"Nature"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1038\/nature05268","article-title":"Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints","volume":"444","author":"Bartkova","year":"2006","journal-title":"Nature"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"7917","DOI":"10.1158\/0008-5472.CAN-08-2510","article-title":"Senescence-associated oxidative DNA damage promotes the generation of neoplastic cells","volume":"69","author":"Gosselin","year":"2009","journal-title":"Cancer Res."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Rader, K. (2004). Making Mice: Standardizing Animals for American Biomedical Research, 1900\u20131955, Princeton University Press.","DOI":"10.1515\/9780691187587"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/2045-3329-2-20","article-title":"Mouse models of sarcomas: Critical tools in our understanding of the pathobiology","volume":"2","author":"Post","year":"2012","journal-title":"Clin. Sarcoma Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1177\/153537020623100713","article-title":"Retinoblastoma tumor suppressor: Where cancer meets the cell cycle","volume":"231","author":"Knudsen","year":"2006","journal-title":"Exp. Biol. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1662","DOI":"10.1101\/gad.1656808","article-title":"Conditional mouse osteosarcoma, dependent on p53 loss and potentiated by loss of Rb, mimics the human disease","volume":"22","author":"Walkley","year":"2008","journal-title":"Genes Dev."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"581","DOI":"10.2174\/138945009788680392","article-title":"The rb pathway and cancer therapeutics","volume":"10","author":"Du","year":"2009","journal-title":"Curr. Drug Targets"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Huang, M.-F., Wang, Y.-X., Chou, Y.-T., and Lee, D.-F. (2024). Therapeutic Strategies for RB1-Deficient Cancers: Intersecting Gene Regulation and Targeted Therapy. Cancers, 16.","DOI":"10.20944\/preprints202403.1011.v1"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1038\/371257a0","article-title":"p15INK4B is a potentia| effector of TGF-\u03b2-induced cell cycle arrest","volume":"371","author":"Hannon","year":"1994","journal-title":"Nature"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1093\/carcin\/bgs003","article-title":"p15 INK4b plays a crucial role in murine lymphoid development and tumorigenesis","volume":"33","author":"Pellicer","year":"2012","journal-title":"Carcinogenesis"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"A117","DOI":"10.1088\/0952-4746\/22\/3A\/321","article-title":"Cancer induction by radiotherapy: Dose dependence and spatial relationship to irradiated volume","volume":"22","author":"Herrmann","year":"2002","journal-title":"J. Radiol. Prot."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"214","DOI":"10.2307\/3577890","article-title":"Frequent chest X-ray fluoroscopy and breast cancer incidence among tuberculosis patients in Massachusetts","volume":"125","author":"Boice","year":"1991","journal-title":"Radiat. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1080\/09553002.2018.1547441","article-title":"Sex-specific lung cancer risk among radiation workers in the million-person study and patients TB-Fluoroscopy","volume":"98","author":"Boice","year":"2022","journal-title":"Int. J. Radiat. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"439","DOI":"10.21037\/atm.2019.09.01","article-title":"Risk of second primary malignancy after non-small cell lung cancer: A competing risk nomogram based on the SEER database","volume":"7","author":"Zhou","year":"2019","journal-title":"Ann. Transl. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.canlet.2013.09.018","article-title":"Abscopal effects of radiation therapy: A clinical review for the radiobiologist","volume":"356","author":"Siva","year":"2015","journal-title":"Cancer Lett."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1038\/nrc2603","article-title":"Radiation-induced bystander signalling in cancer therapy","volume":"9","author":"Prise","year":"2009","journal-title":"Nat. Rev. Cancer"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.2217\/fon-2020-0994","article-title":"The abscopal effect of radiation therapy","volume":"17","author":"Craig","year":"2021","journal-title":"Future Oncol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1016\/j.freeradbiomed.2013.07.024","article-title":"Effects of ionizing radiation on mitochondria","volume":"65","author":"Kam","year":"2013","journal-title":"Free Radic. Biol. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1016\/j.it.2019.10.008","article-title":"Emerging role of mitochondrial DNA as a major driver of inflammation and disease progression","volume":"40","author":"Zhong","year":"2019","journal-title":"Trends Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Averbeck, D., and Rodriguez-Lafrasse, C. (2021). Role of mitochondria in radiation responses: Epigenetic, metabolic, and signaling impacts. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222011047"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1080\/095530097143644","article-title":"Radiation damage to cell membranes: Insights from the oxygen effect","volume":"71","author":"Gillies","year":"1997","journal-title":"Int. J. Radiat. Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1093\/carcin\/bgp008","article-title":"Death receptor pathways mediate targeted and non-targeted effects of ionizing radiations in breast cancer cells","volume":"30","author":"Luce","year":"2009","journal-title":"Carcinogenesis"},{"key":"ref_53","first-page":"6394","article-title":"Induction of sister chromatid exchanges by extremely low doses of \u03b1-particles","volume":"52","author":"Nagasawa","year":"1992","journal-title":"Cancer Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"552","DOI":"10.2307\/3580153","article-title":"Unexpected sensitivity to the induction of mutations by very low doses of alpha-particle radiation: Evidence for a bystander effect","volume":"152","author":"Nagasawa","year":"1999","journal-title":"Radiat. Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1080\/095530098141087","article-title":"Studies of bystander effects in human fibroblasts using a charged particle microbeam","volume":"74","author":"Prise","year":"1998","journal-title":"Int. J. Radiat. Biol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1667\/0033-7587(2003)159[0567:NADEOE]2.0.CO;2","article-title":"Non-targeted and delayed effects of exposure to ionizing radiation: I. Radiation-induced genomic instability and bystander effects in vitro","volume":"159","author":"Morgan","year":"2003","journal-title":"Radiat. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1667\/0033-7587(2003)159[0581:NADEOE]2.0.CO;2","article-title":"Non-targeted and delayed effects of exposure to ionizing radiation: II. Radiation-induced genomic instability and bystander effects in vivo, clastogenic factors and transgenerational effects","volume":"159","author":"Morgan","year":"2003","journal-title":"Radiat. Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.mrrev.2012.12.001","article-title":"Non-targeted effects of ionising radiation\u2014Implications for low dose risk","volume":"752","author":"Kadhim","year":"2013","journal-title":"Mutat. Res. Rev. Mutat. Res."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Mothersill, C., Rusin, A., and Seymour, C. (2019). Relevance of non-targeted effects for radiotherapy and diagnostic radiology; a historical and conceptual analysis of key players. Cancers, 11.","DOI":"10.20944\/preprints201906.0231.v1"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1054\/bjoc.2000.1665","article-title":"Direct evidence for a bystander effect of ionizing radiation in primary human fibroblasts","volume":"84","author":"Belyakov","year":"2001","journal-title":"Br. J. Cancer"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1667\/RR2036.1","article-title":"Serum serotonin levels determine the magnitude and type of bystander effects in medium transfer experiments","volume":"174","author":"Mothersill","year":"2010","journal-title":"Radiat. Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"777","DOI":"10.3109\/09553002.2012.703364","article-title":"The impact of serotonin on the development of bystander damage assessed by \u03b3-H2AX foci analysis","volume":"88","author":"Klammer","year":"2012","journal-title":"Int. J. Radiat. Biol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1128\/JVI.01574-14","article-title":"Structure-function relationships underlying the replication fidelity of viral RNA-dependent RNA polymerases","volume":"89","author":"Campagnola","year":"2015","journal-title":"J. Virol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.mrfmmm.2011.09.002","article-title":"Mechanisms of cadmium induced genomic instability","volume":"733","year":"2012","journal-title":"Mutat. Res. Fundam. Mol. Mech. Mutagen."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1177\/0960327112445937","article-title":"Cadmium-induced genetic instability in mice testis","volume":"31","author":"Oliveira","year":"2012","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"7262","DOI":"10.1073\/pnas.77.12.7262","article-title":"Relationship between X-ray exposure and malignant transformation in C3H 10T1\/2 cells","volume":"77","author":"Kennedy","year":"1980","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_67","first-page":"1161","article-title":"C3H-A uv\u2014A High Hepatoma and High Mammary Tumor Strain of Mice","volume":"40","author":"Heston","year":"1968","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1038\/380683a0","article-title":"Human minisatellite mutation rate after the Chernobyl accident","volume":"380","author":"Dubrova","year":"1996","journal-title":"Nature"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1086\/342729","article-title":"Elevated minisatellite mutation rate in the post-Chernobyl families from Ukraine","volume":"71","author":"Dubrova","year":"2002","journal-title":"Am. J. Hum. Genet."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/S0027-5107(00)00068-3","article-title":"Induction of minisatellite mutations in the mouse germline by low-dose chronic exposure to \u03b3-radiation and fission neutrons","volume":"453","author":"Dubrova","year":"2000","journal-title":"Mutat. Res. Fundam. Mol. Mech. Mutagen."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/S0936-6555(05)80035-4","article-title":"Normal tissue radiosensitivity\u2014How important is it?","volume":"8","author":"Burnet","year":"1996","journal-title":"Clin. Oncol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1007\/s00520-004-0697-z","article-title":"Late sequelae of radiotherapy in adults","volume":"13","author":"Mohanti","year":"2005","journal-title":"Support. Care Cancer"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1002\/(SICI)1097-0215(19981218)79:6<606::AID-IJC9>3.0.CO;2-Y","article-title":"Describing patients\u2019 normal tissue reactions: Concerning the possibility of individualising radiotherapy dose prescriptions based on potential predictive assays of normal tissue radiosensitivity","volume":"79","author":"Burnet","year":"1998","journal-title":"Int. J. Cancer"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Pereira, S., Orlandi, E., Deneuve, S., Barcellini, A., Chalaszczyk, A., Behm-Ansmant, I., Hettal, L., Rancati, T., Vogin, G., and Thariat, J. (2022). The normal, the radiosensitive, and the ataxic in the era of precision radiotherapy: A narrative review. Cancers, 14.","DOI":"10.3390\/cancers14246252"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"S840","DOI":"10.21037\/tcr.2017.06.45","article-title":"Normal tissue tolerance","volume":"6","author":"Herrmann","year":"2017","journal-title":"Transl. Cancer Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1016\/S0360-3016(96)00426-9","article-title":"Prognostic factors for acute and late skin reactions in radiotheraphy patients","volume":"36","author":"Turesson","year":"1996","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.mrrev.2016.09.001","article-title":"Individual response to ionizing radiation","volume":"770","author":"Foray","year":"2016","journal-title":"Mutat. Res. Rev. Mutat. Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1177\/0146645315623158","article-title":"Evidence for variation in human radiosensitivity and its potential impact on radiological protection","volume":"45","author":"Bouffler","year":"2016","journal-title":"Ann. ICRP"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1182\/blood.V83.2.596.596","article-title":"Hematopoietic Recovery After 10-Gy Acute Total Body Radiation","volume":"83","author":"Baranov","year":"1994","journal-title":"Blood"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1016\/j.ijrobp.2009.02.057","article-title":"Clinical radiation sensitivity with DNA repair disorders: An overview","volume":"74","author":"Pollard","year":"2009","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_81","first-page":"239","article-title":"Excess of rare cancers in Werner syndrome (adult progeria)","volume":"5","author":"Goto","year":"1996","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_82","first-page":"119","article-title":"Radiotherapy and radiosensitivity syndromes in DNA repair gene mutations","volume":"35","year":"2022","journal-title":"Klin. Onkol. Cas. Ceske A Slov. Onkol. Spol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.clon.2004.01.011","article-title":"Clinical and cellular radiosensitivity in inherited human syndromes","volume":"16","author":"Leong","year":"2004","journal-title":"Clin. Oncol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.ceb.2015.05.007","article-title":"DNA repair defects and genome instability in Hutchinson\u2013Gilford progeria syndrome","volume":"34","author":"Gonzalo","year":"2015","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1038\/nature02118","article-title":"A DNA damage checkpoint response in telomere-initiated senescence","volume":"426","author":"Fagagna","year":"2003","journal-title":"Nature"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1038\/nrg1656","article-title":"Telomeres and human disease: Ageing, cancer and beyond","volume":"6","author":"Blasco","year":"2005","journal-title":"Nat. Rev. Genet."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"20170949","DOI":"10.1259\/bjr.20170949","article-title":"Radiation biology and oncology in the genomic era","volume":"91","author":"Kerns","year":"2018","journal-title":"Br. J. Radiol."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Seegenschmiedt, M.H., Makoski, H.B., Trott, K.R., and Brady, L.W. (2008). Radiotherapy for Non-Malignant Disorders, Springer.","DOI":"10.1007\/978-3-540-68943-0"},{"key":"ref_89","unstructured":"Mould, R.F. (1980). A History of X-Rays and Radium: With a Chapter on Radiation Units: 1895\u20131937, IPC Building & Contract Journals."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Homei, A., and Worboys, M. (2013). Fungal disease in Britain and the United States 1850\u20132000: Mycoses and Modernity, Springer Nature.","DOI":"10.26530\/OAPEN_474551"},{"key":"ref_91","first-page":"7","article-title":"Benign and malignant thyroid neoplasms after childhood irradiation for tinea capitis","volume":"65","author":"Ron","year":"1980","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1016\/S1473-3099(10)70107-9","article-title":"The tinea capitis campaign in Serbia in the 1950s","volume":"10","author":"Shvarts","year":"2010","journal-title":"Lancet Infect. Dis."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1093\/jnci\/77.3.689","article-title":"Breast cancer among women given X-ray therapy for acute postpartum mastitis","volume":"77","author":"Shore","year":"1986","journal-title":"JNCI J. Natl. Cancer Inst."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1002\/ijc.2910590307","article-title":"Cancer mortality following X-ray treatment for ankylosing spondylitis","volume":"59","author":"Weiss","year":"1994","journal-title":"Int. J. Cancer"},{"key":"ref_95","first-page":"1","article-title":"Functional and molecular aspects of anti-inflammatory effects of low-dose radiotherapy","volume":"178","author":"Kamprad","year":"2002","journal-title":"Strahlenther. Onkol. Organ Dtsch. Rontgenges."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1191\/096032700678815602","article-title":"Radiation hormesis: Its historical foundations as a biological hypothesis","volume":"19","author":"Calabrese","year":"2000","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_97","first-page":"338","article-title":"De l\u2019influence des rayons X sur la vegetation","volume":"159","author":"Miege","year":"1914","journal-title":"Compt. Rend. Acad. Sci."},{"key":"ref_98","first-page":"100","article-title":"On the effect of Roentgen rays upon seeds of Oryza sativa","volume":"6","author":"Yamada","year":"1917","journal-title":"J. Phys. Ther."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"242","DOI":"10.2967\/jnmt.115.166074","article-title":"Radiation hormesis: Historical and current perspectives","volume":"43","author":"Baldwin","year":"2015","journal-title":"J. Nucl. Med. Technol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1191\/096032700678815611","article-title":"Radiation hormesis: The demise of a legitimate hypothesis","volume":"19","author":"Calabrese","year":"2000","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1002\/jez.1400280305","article-title":"Prolongation of life of Tribolium confusum apparently due to small doses of X-rays","volume":"28","author":"Davey","year":"1919","journal-title":"J. Exp. Zool."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"551","DOI":"10.2307\/3570571","article-title":"Gamma-radiation and longevity of the flour beetle","volume":"7","author":"Cork","year":"1957","journal-title":"Radiat. Res."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1259\/bjr\/63353075","article-title":"Evidence for beneficial low level radiation effects and radiation hormesis","volume":"78","author":"Feinendegen","year":"2005","journal-title":"Br. J. Radiol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.it.2019.02.002","article-title":"The cellular immunotherapy revolution: Arming the immune system for precision therapy","volume":"40","author":"Paucek","year":"2019","journal-title":"Trends Immunol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"3044","DOI":"10.3390\/curroncol29050247","article-title":"Immune checkpoint inhibitors in cancer therapy","volume":"29","author":"Shiravand","year":"2022","journal-title":"Curr. Oncol."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Sevenich, L. (2019). Turning \u201ccold\u201d into \u201chot\u201d tumors\u2014Opportunities and challenges for radio-immunotherapy against primary and metastatic brain cancers. Front. Oncol., 9.","DOI":"10.3389\/fonc.2019.00163"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/1\/257\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:57:22Z","timestamp":1760115442000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/1\/257"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,30]]},"references-count":106,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,1]]}},"alternative-id":["ijms26010257"],"URL":"https:\/\/doi.org\/10.3390\/ijms26010257","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,30]]}}}