{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:50:45Z","timestamp":1790779845978,"version":"4.1.0"},"reference-count":86,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2022,9,9]],"date-time":"2022-09-09T00:00:00Z","timestamp":1662681600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Commissariat General \u00e0 l\u2019Investissement"},{"name":"Institut National du Cancer (InCa)"},{"name":"National Space Agency (CNES)"},{"name":"French-Lebanon partenariat Hubert Curien"},{"name":"R\u00e9gion Auvergne Rh\u00f4ne-Alpes"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Tissue overreactions (OR), whether called adverse effects, radiotoxicity, or radiosensitivity reactions, may occur during or after anti-cancer radiotherapy (RT). They represent a medical, economic, and societal issue and raise the question of individual response to radiation. To predict and prevent them are among the major tasks of radiobiologists. To this aim, radiobiologists have developed a number of predictive assays involving different cellular models and endpoints. To date, while no consensus has been reached to consider one assay as the best predictor of the OR occurrence and severity, radiation oncologists have proposed consensual scales to quantify OR in six different grades of severity, whatever the organ\/tissue concerned and their early\/late features. This is notably the case with the Common Terminology Criteria for Adverse Events (CTCAE). Few radiobiological studies have used the CTCAE scale as a clinical endpoint to evaluate the statistical robustness of the molecular and cellular predictive assays in the largest range of human radiosensitivity. Here, by using 200 untransformed skin fibroblast cell lines derived from RT-treated cancer patients eliciting OR in the six CTCAE grades range, correlations between CTCAE grades and the major molecular and cellular endpoints proposed to predict OR (namely, cell survival at 2 Gy (SF2), yields of micronuclei, recognized and unrepaired DSBs assessed by immunofluorescence with \u03b3H2AX and pATM markers) were examined. To our knowledge, this was the first time that the major radiosensitivity endpoints were compared together with the same cohort and irradiation conditions. Both SF2 and the maximal number of pATM foci reached after 2 Gy appear to be the best predictors of the OR, whatever the CTCAE grades range. All these major radiosensitivity endpoints are mathematically linked in a single mechanistic model of individual response to radiation in which the ATM kinase plays a major role.<\/jats:p>","DOI":"10.3390\/ijms231810434","type":"journal-article","created":{"date-parts":[[2022,9,9]],"date-time":"2022-09-09T04:54:41Z","timestamp":1662699281000},"page":"10434","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Quantitative Correlations between Radiosensitivity Biomarkers Show That the ATM Protein Kinase Is Strongly Involved in the Radiotoxicities Observed after Radiotherapy"],"prefix":"10.3390","volume":"23","author":[{"given":"Eymeric","family":"Le Reun","sequence":"first","affiliation":[{"name":"Inserm, U1296 Unit, \u00abRadiation: Defense, Health and Environment\u00bb, Centre L\u00e9on-B\u00e9rard, 28, rue Laennec, 69008 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1067-9435","authenticated-orcid":false,"given":"Larry","family":"Bodgi","sequence":"additional","affiliation":[{"name":"Inserm, U1296 Unit, \u00abRadiation: Defense, Health and Environment\u00bb, Centre L\u00e9on-B\u00e9rard, 28, rue Laennec, 69008 Lyon, France"},{"name":"Department of Radiation Oncology, American University of Beirut Medical Center, Riad El-Solh, Beirut 1107-2020, Lebanon"},{"name":"Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Bliss Street, 11-0236 Riad El-Solh, Beirut 1107-2020, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adeline","family":"Granzotto","sequence":"additional","affiliation":[{"name":"Inserm, U1296 Unit, \u00abRadiation: Defense, Health and Environment\u00bb, Centre L\u00e9on-B\u00e9rard, 28, rue Laennec, 69008 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laur\u00e8ne","family":"Sonzogni","sequence":"additional","affiliation":[{"name":"Inserm, U1296 Unit, \u00abRadiation: Defense, Health and Environment\u00bb, Centre L\u00e9on-B\u00e9rard, 28, rue Laennec, 69008 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e9lanie L.","family":"Ferlazzo","sequence":"additional","affiliation":[{"name":"Inserm, U1296 Unit, \u00abRadiation: Defense, Health and Environment\u00bb, Centre L\u00e9on-B\u00e9rard, 28, rue Laennec, 69008 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6772-6947","authenticated-orcid":false,"given":"Jo\u00eblle","family":"Al-Choboq","sequence":"additional","affiliation":[{"name":"Inserm, U1296 Unit, \u00abRadiation: Defense, Health and Environment\u00bb, Centre L\u00e9on-B\u00e9rard, 28, rue Laennec, 69008 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2860-9235","authenticated-orcid":false,"given":"Laura","family":"El-Nachef","sequence":"additional","affiliation":[{"name":"Inserm, U1296 Unit, \u00abRadiation: Defense, Health and Environment\u00bb, Centre L\u00e9on-B\u00e9rard, 28, rue Laennec, 69008 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliette","family":"Restier-Verlet","sequence":"additional","affiliation":[{"name":"Inserm, U1296 Unit, \u00abRadiation: Defense, Health and Environment\u00bb, Centre L\u00e9on-B\u00e9rard, 28, rue Laennec, 69008 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7057-1840","authenticated-orcid":false,"given":"Elise","family":"Berthel","sequence":"additional","affiliation":[{"name":"Inserm, U1296 Unit, \u00abRadiation: Defense, Health and Environment\u00bb, Centre L\u00e9on-B\u00e9rard, 28, rue Laennec, 69008 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7622-9886","authenticated-orcid":false,"given":"Cl\u00e9ment","family":"Devic","sequence":"additional","affiliation":[{"name":"Inserm, U1296 Unit, \u00abRadiation: Defense, Health and Environment\u00bb, Centre L\u00e9on-B\u00e9rard, 28, rue Laennec, 69008 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7228-8830","authenticated-orcid":false,"given":"Audrey","family":"Bouchet","sequence":"additional","affiliation":[{"name":"Inserm, U1296 Unit, \u00abRadiation: Defense, Health and Environment\u00bb, Centre L\u00e9on-B\u00e9rard, 28, rue Laennec, 69008 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Bourguignon","sequence":"additional","affiliation":[{"name":"Inserm, U1296 Unit, \u00abRadiation: Defense, Health and Environment\u00bb, Centre L\u00e9on-B\u00e9rard, 28, rue Laennec, 69008 Lyon, France"},{"name":"Department of Biophysics and Nuclear Medicine, Universit\u00e9 Paris Saclay Versailles St. Quentin en Yvelines, 78035 Versailles, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1282-1303","authenticated-orcid":false,"given":"Nicolas","family":"Foray","sequence":"additional","affiliation":[{"name":"Inserm, U1296 Unit, \u00abRadiation: Defense, Health and Environment\u00bb, Centre L\u00e9on-B\u00e9rard, 28, rue Laennec, 69008 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,9]]},"reference":[{"key":"ref_1","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 radiotherapy patients","volume":"36","author":"Turesson","year":"1996","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"ICRP Publication 105 (2007). Radiation protection in medicine. Ann. ICRP, 37, 1\u201363.","DOI":"10.1016\/j.icrp.2008.07.001"},{"key":"ref_3","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."},{"key":"ref_4","first-page":"96","article-title":"Skin and other reactions to radiotherapy\u2014Clinical presentation and radiobiology of skin reactions","volume":"39","author":"Dorr","year":"2006","journal-title":"Front. Radiat. Ther. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.icrp.2012.02.001","article-title":"ICRP publication 118: ICRP statement on tissue reactions and early and late effects of radiation in normal tissues and organs\u2014Threshold doses for tissue reactions in a radiation protection context","volume":"41","author":"Stewart","year":"2012","journal-title":"Ann. ICRP"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1016\/0360-3016(95)00060-C","article-title":"Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC)","volume":"31","author":"Cox","year":"1995","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/S1470-2045(03)01191-4","article-title":"Effects of radiation on normal tissue: Consequences and mechanisms","volume":"4","author":"Stone","year":"2003","journal-title":"Lancet Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.jpainsymman.2019.03.017","article-title":"The Impact of Radiodermatitis on Breast Cancer Patients\u2019 Quality of Life during Radiotherapy: A Prospective Cohort Study","volume":"58","author":"Fuzissaki","year":"2019","journal-title":"J. Pain Symptom Manag."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1002\/cncr.25467","article-title":"Ten-year outcomes of high-dose, intensity-modulated radiotherapy for localized prostate cancer","volume":"117","author":"Alicikus","year":"2011","journal-title":"Cancer"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1016\/j.ijrobp.2016.03.024","article-title":"Simple Factors Associated with Radiation-Induced Lung Toxicity after Stereotactic Body Radiation Therapy of the Thorax: A Pooled Analysis of 88 Studies","volume":"95","author":"Zhao","year":"2016","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1080\/09553002.2019.1704908","article-title":"Establishing mechanisms affecting the individual response to ionizing radiation","volume":"96","author":"Averbeck","year":"2020","journal-title":"Int. J. Radiat. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/j.semradonc.2017.04.003","article-title":"Functional Assays for Individual Radiosensitivity: A Critical Review","volume":"27","author":"Ferlazzo","year":"2017","journal-title":"Semin. Radiat. Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1016\/j.clon.2007.06.011","article-title":"Lessons from Epinal","volume":"19","author":"Ash","year":"2007","journal-title":"Clin. Oncol."},{"key":"ref_14","first-page":"309","article-title":"Epinal radiotherapy accident: Passed, present, future","volume":"11","author":"Peiffert","year":"2007","journal-title":"Cancer Radiother. J. Soc. Fr. Radiother. Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"El-Nachef, L., Al-Choboq, J., Restier-Verlet, J., Granzotto, A., Berthel, E., Sonzogni, L., Ferlazzo, M.L., Bouchet, A., Leblond, P., and Combemale, P. (2021). Human Radiosensitivity and Radiosusceptibility: What Are the Differences?. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22137158"},{"key":"ref_16","unstructured":"National Institutes of Health, and National Cancer Institute (2010). Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. May 28, 2009 (v4.03: June 14, 2010)."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/S1053-4296(03)00031-6","article-title":"CTCAE v3.0: Development of a comprehensive grading system for the adverse effects of cancer treatment","volume":"13","author":"Trotti","year":"2003","journal-title":"Semin. Radiat. Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/S1470-2045(11)70302-3","article-title":"Independent validation of genes and polymorphisms reported to be associated with radiation toxicity: A prospective analysis study","volume":"13","author":"Barnett","year":"2012","journal-title":"Lancet Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.radonc.2014.02.012","article-title":"A genome wide association study (GWAS) providing evidence of an association between common genetic variants and late radiotherapy toxicity","volume":"111","author":"Barnett","year":"2014","journal-title":"Radiother. Oncol. J. Eur. Soc. Ther. Radiol. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1845","DOI":"10.1038\/sj.bjc.6604381","article-title":"Aberrant CDKN1A transcriptional response associates with abnormal sensitivity to radiation treatment","volume":"98","author":"Badie","year":"2008","journal-title":"Br. J. Cancer"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1667\/RR3236.1","article-title":"Laboratory intercomparison of gene expression assays","volume":"180","author":"Badie","year":"2013","journal-title":"Radiat. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/0360-3016(95)02029-2","article-title":"A review of human cell radiosensitivity in vitro","volume":"34","author":"Deschavanne","year":"1996","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"73","DOI":"10.2307\/3576448","article-title":"Mean inactivation dose: A useful concept for intercomparison of human cell survival curves","volume":"99","author":"Fertil","year":"1984","journal-title":"Radiat. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/0360-3016(81)90377-1","article-title":"Inherent cellular radiosensitivity as a basic concept for human tumor radiotherapy","volume":"7","author":"Fertil","year":"1981","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1080\/095530099139430","article-title":"Relationships between colony forming efficiency and parameters of intrinsic radiosensitivity","volume":"75","author":"Fertil","year":"1999","journal-title":"Int. J. Radiat. Biol."},{"key":"ref_26","first-page":"4705","article-title":"Radiation sensitivity of cell strains from families with genetic disorders predisposing to radiation-induced cancer","volume":"49","author":"Little","year":"1989","journal-title":"Cancer Res."},{"key":"ref_27","first-page":"926","article-title":"Survey of radiosensitivity in a variety of human cell strains","volume":"40","author":"Arlett","year":"1980","journal-title":"Cancer Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/S0027-5107(00)00065-8","article-title":"The in vitro micronucleus technique","volume":"455","author":"Fenech","year":"2000","journal-title":"Mutat. Res."},{"key":"ref_29","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."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1080\/09553000701797039","article-title":"DNA double-strand break repair defects in syndromes associated with acute radiation response: At least two different assays to predict intrinsic radiosensitivity?","volume":"84","author":"Joubert","year":"2008","journal-title":"Int. J. Radiat. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/S0300-483X(03)00293-2","article-title":"Molecular mechanisms of individual radiosensitivity studied in normal diploid human fibroblasts","volume":"193","author":"Dikomey","year":"2003","journal-title":"Toxicology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1038\/bjc.1995.62","article-title":"Radiation-induced DNA double-strand break rejoining in human tumour cells","volume":"71","author":"Nunez","year":"1995","journal-title":"Br. J. Cancer"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1038\/bjc.1994.83","article-title":"Initial radiation-induced DNA damage in human tumour cell lines: A correlation with intrinsic cellular radiosensitivity","volume":"69","author":"Nunez","year":"1994","journal-title":"Br. J. Cancer"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"385","DOI":"10.2307\/3576926","article-title":"A quantitative comparison of potentially lethal damage repair and the rejoining of interphase chromosome breaks in low passage normal human fibroblasts","volume":"111","author":"Cornforth","year":"1987","journal-title":"Radiat. Res."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Abujamra, A.L. (2011). DNA double-strand breaks repair and signaling of human gliomas and normal brain cells in response to radiation: Potential impact of the ATM- and BRCA1-dependent pathways. Brain Tumors\u2014Current and Emerging Therapeutic Strategies, Intechweb.","DOI":"10.5772\/1048"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1002\/bies.950131204","article-title":"The role of DNA double strand breaks in ionizing radiation-induced killing of eukaryotic cells","volume":"13","author":"Iliakis","year":"1991","journal-title":"BioEssays News Rev. Mol. Cell. Dev. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"7717","DOI":"10.1038\/sj.onc.1210868","article-title":"DNA double-strand breaks: Their cellular and clinical impact?","volume":"26","author":"Jeggo","year":"2007","journal-title":"Oncogene"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"5678","DOI":"10.1093\/nar\/gkn550","article-title":"Gamma-H2AX in recognition and signaling of DNA double-strand breaks in the context of chromatin","volume":"36","author":"Kinner","year":"2008","journal-title":"Nucleic Acids Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1080\/09553009514551411","article-title":"A cell-free assay using cytoplasmic cell extracts to study rejoining of radiation-induced DNA double-strand breaks in human cell nuclei","volume":"68","author":"Ganguly","year":"1995","journal-title":"Int. J. Radiat. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Berthel, E., Ferlazzo, M.L., Devic, C., Bourguignon, M., and Foray, N. (2019). What does the History of Research on the Repair of DNA Double-Strand Breaks Tell Us?\u2014A Comprehensive Review of Human Radiosensitivity. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20215339"},{"key":"ref_41","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_42","doi-asserted-by":"crossref","unstructured":"Berthel, E., Foray, N., and Ferlazzo, M.L. (2019). The Nucleoshuttling of the ATM Protein: A Unified Model to Describe the Individual Response to High- and Low-Dose of Radiation?. Cancers, 11.","DOI":"10.3390\/cancers11070905"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.ijrobp.2015.11.013","article-title":"Influence of Nucleoshuttling of the ATM Protein in the Healthy Tissues Response to Radiation Therapy: Toward a Molecular Classification of Human Radiosensitivity","volume":"94","author":"Granzotto","year":"2016","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.radonc.2005.06.027","article-title":"The two edges of the ATM sword: Co-operation between repair and checkpoint functions","volume":"76","author":"Lobrich","year":"2005","journal-title":"Radiother. Oncol. J. Eur. Soc. Ther. Radiol. Oncol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1038\/258427a0","article-title":"Ataxia telangiectasia: A human mutation with abnormal radiation sensitivity","volume":"258","author":"Taylor","year":"1975","journal-title":"Nature"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2860","DOI":"10.1093\/emboj\/cdg274","article-title":"A subset of ATM- and ATR-dependent phosphorylation events requires the BRCA1 protein","volume":"22","author":"Foray","year":"2003","journal-title":"EMBO J."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1016\/j.ijrobp.2018.03.047","article-title":"The Phosphorylated ATM Immunofluorescence Assay: A High-performance Radiosensitivity Assay to Predict Postradiation Therapy Overreactions","volume":"101","author":"Vogin","year":"2018","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.ijrobp.2017.10.029","article-title":"Fast and binary assay for predicting radiosensitivity based on the nucleoshuttling of ATM protein: Development, validation and performances","volume":"100","author":"Pereira","year":"2018","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"117","DOI":"10.3109\/09553002.2016.1135260","article-title":"The nucleo-shuttling of the ATM protein as a basis for a novel theory of radiation response: Resolution of the linear-quadratic model","volume":"92","author":"Bodgi","year":"2016","journal-title":"Int. J. Radiat. Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.jtbi.2016.01.018","article-title":"Mathematical models of radiation action on living cells: From the target theory to the modern approaches. A historical and critical review","volume":"394","author":"Bodgi","year":"2016","journal-title":"J. Theor. Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1080\/09553008114550491","article-title":"Observations of radiation-induced chromosome fragment loss in live mammalian cells in culture, and its effect on colony-forming ability","volume":"39","author":"Grote","year":"1981","journal-title":"Int. J. Radiat. Biol. Relat. Stud. Phys. Chem. Med."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Al-Choboq, J., Ferlazzo, M.L., Sonzogni, L., Granzotto, A., El-Nachef, L., Maalouf, M., Berthel, E., and Foray, N. (2022). Usher Syndrome Belongs to the Genetic Diseases Associated with Radiosensitivity: Influence of the ATM Protein Kinase. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23031570"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1007\/s12035-021-02615-3","article-title":"Individual Response to Radiation of Individuals with Neurofibromatosis Type I: Role of the ATM Protein and Influence of Statins and Bisphosphonates","volume":"59","author":"Combemale","year":"2022","journal-title":"Mol. Neurobiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1080\/09553002.2020.1694189","article-title":"Some mutations in the xeroderma pigmentosum D gene may lead to moderate but significant radiosensitivity associated with a delayed radiation-induced ATM nuclear localization","volume":"96","author":"Ferlazzo","year":"2019","journal-title":"Int. J. Radiat. Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"5858","DOI":"10.1074\/jbc.273.10.5858","article-title":"DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139","volume":"273","author":"Rogakou","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1667\/0033-7587(2002)158[0486:QDOIID]2.0.CO;2","article-title":"Quantitative detection of (125)IdU-induced DNA double-strand breaks with gamma-H2AX antibody","volume":"158","author":"Sedelnikova","year":"2002","journal-title":"Radiat. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"42462","DOI":"10.1074\/jbc.C100466200","article-title":"ATM phosphorylates histone H2AX in response to DNA double-strand breaks","volume":"276","author":"Burma","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"5706","DOI":"10.1128\/MCB.23.16.5706-5715.2003","article-title":"Pathways of DNA double-strand break repair during the mammalian cell cycle","volume":"23","author":"Rothkamm","year":"2003","journal-title":"Mol. Cell. Biol."},{"key":"ref_59","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":"Kuhne","year":"2004","journal-title":"Cancer Res."},{"key":"ref_60","first-page":"4600","article-title":"A DNA double-strand break defective fibroblast cell line (180BR) derived from a radiosensitive patient represents a new mutant phenotype","volume":"57","author":"Badie","year":"1997","journal-title":"Cancer Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"26","DOI":"10.2307\/3579232","article-title":"Induction and rejoining of DNA double-strand breaks and interphase chromosome breaks after exposure to X rays in one normal and two hypersensitive human fibroblast cell lines","volume":"144","author":"Badie","year":"1995","journal-title":"Radiat. Res."},{"key":"ref_62","first-page":"1232","article-title":"Defective repair of DNA double-strand breaks and chromosome damage in fibroblasts from a radiosensitive leukemia patient","volume":"55","author":"Badie","year":"1995","journal-title":"Cancer Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1016\/j.ijrobp.2009.12.055","article-title":"Clinical implications of the tumor volume reduction rate in head-and-neck cancer during definitive intensity-modulated radiotherapy for organ preservation","volume":"79","author":"Yang","year":"2011","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_64","first-page":"295","article-title":"Does the radiation approach affect acute toxicity in prostate cancer patients? A comparison of four radiation techniques","volume":"73","author":"Chomiak","year":"2020","journal-title":"Cent. Eur. J. Urol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1078\/0939-3889-00193","article-title":"Future trends in cancer therapy with particle accelerators","volume":"14","author":"Amaldi","year":"2004","journal-title":"Z. Med. Phys."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Le Reun, E., Casutt, A., Durham, A., Bouchaab, H., Romano, E., Lovis, A., Krueger, T., Von Garnier, C., Ozshahin, E.M., and Kinj, R. Lung stereotactic radiation therapy: Intercomparison of irradiation devices in terms of outcome and predictive factors. Cancer Radiother. J. Soc. Fr. Radiother. Oncol., 2022. in press.","DOI":"10.21203\/rs.3.rs-1213819\/v1"},{"key":"ref_67","first-page":"684","article-title":"Prognostic factors of acute radiodermatitis in breast cancer after adjuvant radiotherapy treated with RT3D or IMRT","volume":"26","author":"Thomas","year":"2022","journal-title":"Cancer Radiother. J. Soc. Fr. Radiother. Oncol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.ijrobp.2022.05.041","article-title":"A Comparison of Patient- and Clinician-Reported Acute Toxicity during Radiotherapy for Primary Breast Cancer","volume":"114","author":"Lapen","year":"2022","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_69","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_70","unstructured":"Elkind, M.M., and Whitmore, G.F. (1967). The Radiobiology of Cultured Mammalian Cells, Gordon and Breach."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1080\/09553008814552321","article-title":"Comparative human cellular radiosensitivity: I. The effect of SV40 transformation and immortalisation on the gamma-irradiation survival of skin derived fibroblasts from normal individuals and from ataxia-telangiectasia patients and heterozygotes","volume":"54","author":"Arlett","year":"1988","journal-title":"Int. J. Radiat. Biol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"4973","DOI":"10.1007\/s12035-017-0648-6","article-title":"Radiobiological characterization of tuberous sclerosis: A delay in the nucleo-shuttling of ATM may be responsible for radiosensitivity","volume":"55","author":"Ferlazzo","year":"2017","journal-title":"Mol. Neurobiol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1007\/s12035-013-8591-7","article-title":"Mutations of the Huntington\u2019s Disease Protein Impact on the ATM-Dependent Signaling and Repair Pathways of the Radiation-Induced DNA Double-Strand Breaks: Corrective Effect of Statins and Bisphosphonates","volume":"49","author":"Ferlazzo","year":"2014","journal-title":"Mol. Neurobiol."},{"key":"ref_74","first-page":"546","article-title":"Fibroblasts from Retinoblastoma Patients Show Radiosensitivity Linked to Abnormal Localization of the ATM Protein","volume":"46","author":"Ferlazzo","year":"2020","journal-title":"Curr. Eye Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.26502\/acmcr.96550297","article-title":"First Radiobiological Characterization of Skin and Bone Cells from a Patient Suffering from the PI3KCA-Related Overgrowth Spectrum (PROS) Syndrome","volume":"4","author":"Bachelet","year":"2020","journal-title":"Arch. Med. Clin. Case Rep."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1080\/09553002.2021.1864045","article-title":"First radiobiological characterization of the McCune-Albright syndrome: Influence of the ATM protein and effect of statins + bisphosphonates treatment","volume":"97","author":"Bachelet","year":"2021","journal-title":"Int. J. Radiat. Biol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1016\/j.ijrobp.2015.02.023","article-title":"Survival Fraction at 2 Gy and gammaH2AX Expression Kinetics in Peripheral Blood Lymphocytes from Cancer Patients: Relationship with Acute Radiation-Induced Toxicities","volume":"92","author":"Pouliliou","year":"2015","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_78","first-page":"564","article-title":"Increased radiosensitivity in a child with T-cell non-Hodgkin\u2019s lymphoma","volume":"27","author":"Saha","year":"1996","journal-title":"Med. Pediatr. Oncol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1259\/0007-1285-63-752-624","article-title":"An instance of clinical radiation morbidity and cellular radiosensitivity, not associated with ataxia-telangiectasia","volume":"63","author":"Plowman","year":"1990","journal-title":"Br. J. Radiol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"e28","DOI":"10.1097\/MPH.0b013e3181bfd3d9","article-title":"Ataxia-telangiectasia with hyper-IgM and Wilms tumor: Fatal reaction to irradiation","volume":"32","author":"Pietrucha","year":"2010","journal-title":"J. Pediatr. Hematol. Oncol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1038\/bjc.1998.98","article-title":"Radiation-induced micronucleus induction in lymphocytes identifies a high frequency of radiosensitive cases among breast cancer patients: A test for predisposition?","volume":"77","author":"Scott","year":"1998","journal-title":"Br. J. Cancer"},{"key":"ref_82","first-page":"390","article-title":"Induced micronucleus frequencies in peripheral lymphocytes as a screening test for carriers of a BRCA1 mutation in breast cancer families","volume":"60","author":"Rothfuss","year":"2000","journal-title":"Cancer Res."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Sommer, S., Buraczewska, I., and Kruszewski, M. (2020). Micronucleus Assay: The State of Art, and Future Directions. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21041534"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1002\/ajmg.10688","article-title":"Chromosome breakage syndromes and cancer","volume":"115","author":"Duker","year":"2002","journal-title":"Am. J. Med. Genet."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"406","DOI":"10.2307\/3576927","article-title":"Relationship between the recovery from sublethal X-ray damage and the rejoining of chromosome breaks in normal human fibroblasts","volume":"111","author":"Bedford","year":"1987","journal-title":"Radiat. Res."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1080\/095530097143266","article-title":"Hypersensitivity of ataxia telangiectasia fibroblasts to ionizing radiation is associated with a repair deficiency of DNA double-strand breaks","volume":"72","author":"Foray","year":"1997","journal-title":"Int. J. Radiat. Biol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/18\/10434\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:28:06Z","timestamp":1760142486000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/18\/10434"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,9]]},"references-count":86,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2022,9]]}},"alternative-id":["ijms231810434"],"URL":"https:\/\/doi.org\/10.3390\/ijms231810434","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,9]]}}}