{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:51:13Z","timestamp":1790779873841,"version":"4.1.0"},"reference-count":51,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T00:00:00Z","timestamp":1692576000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Commissariat General \u00e0 l\u2019Investissement"},{"name":"National Space Agency (CNES)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Studies about radiation-induced human cataractogenesis are generally limited by (1) the poor number of epithelial lens cell lines available (likely because of the difficulties of cell sampling and amplification) and (2) the lack of reliable biomarkers of the radiation-induced aging process. We have developed a mechanistic model of the individual response to radiation based on the nucleoshuttling of the ATM protein (RIANS). Recently, in the frame of the RIANS model, we have shown that, to respond to permanent endo- and exogenous stress, the ATM protein progressively agglutinates around the nucleus attracted by overexpressed perinuclear ATM-substrate protein. As a result, perinuclear ATM crowns appear to be an interesting biomarker of aging. The radiobiological characterization of the two human epithelial lens cell lines available and the four porcine epithelial lens cell lines that we have established showed delayed RIANS. The BFSP2 protein, found specifically overexpressed around the lens cell nucleus and interacting with ATM, may be a specific ATM-substrate protein facilitating the formation of perinuclear ATM crowns in lens cells. The perinuclear ATM crowns were observed inasmuch as the number of culture passages is high. Interestingly, 2 Gy X-rays lead to the transient disappearance of the perinuclear ATM crowns. Altogether, our findings suggest a strong influence of the ATM protein in radiation-induced cataractogenesis.<\/jats:p>","DOI":"10.3390\/cells12162118","type":"journal-article","created":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T08:53:31Z","timestamp":1692608011000},"page":"2118","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The Radiobiological Characterization of Human and Porcine Lens Cells Suggests the Importance of the ATM Kinase in Radiation-Induced Cataractogenesis"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6772-6947","authenticated-orcid":false,"given":"Jo\u00eblle","family":"Al-Choboq","sequence":"first","affiliation":[{"name":"INSERM U1296 Unit \u201cRadiation: Defense, Health, Environment\u201d, 28 Rue Laennec, 69008 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1418-1872","authenticated-orcid":false,"given":"Thibaud","family":"Mathis","sequence":"additional","affiliation":[{"name":"Ophtalmology Department, Hospices Civils de Lyon, General University Hospital of Croix-Rousse, 103 Grande Rue Croix Rousse, 69004 Lyon, France"},{"name":"MATEIS Laboratory, CNRS UMR5510, INSA, Universit\u00e9 Claude-Bernard Lyon 1, Campus de la Doua, 69100 Villeurbanne, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliette","family":"Restier-Verlet","sequence":"additional","affiliation":[{"name":"INSERM U1296 Unit \u201cRadiation: Defense, Health, Environment\u201d, 28 Rue Laennec, 69008 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laur\u00e8ne","family":"Sonzogni","sequence":"additional","affiliation":[{"name":"INSERM U1296 Unit \u201cRadiation: Defense, Health, Environment\u201d, 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 \u201cRadiation: Defense, Health, Environment\u201d, 28 Rue Laennec, 69008 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adeline","family":"Granzotto","sequence":"additional","affiliation":[{"name":"INSERM U1296 Unit \u201cRadiation: Defense, Health, Environment\u201d, 28 Rue Laennec, 69008 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4575-5840","authenticated-orcid":false,"given":"Michel","family":"Bourguignon","sequence":"additional","affiliation":[{"name":"INSERM U1296 Unit \u201cRadiation: Defense, Health, Environment\u201d, 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 \u201cRadiation: Defense, Health, Environment\u201d, 28 Rue Laennec, 69008 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,21]]},"reference":[{"key":"ref_1","unstructured":"Haye, C., Jammet, H., and Dollfus, M. (1963). L\u2019oeil et les Radiations Ionisantes, Masson."},{"key":"ref_2","first-page":"886","article-title":"Ueber die Wirkung der Rontgenstrahlen auf das Auge und die Haut","volume":"21","author":"Chalupecky","year":"1897","journal-title":"Zent. F. Prakt. Augenh."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1056\/NEJM190304021481404","article-title":"This effect of X-Light on the crystalline lens","volume":"148","author":"Rollins","year":"1903","journal-title":"Boston Med. Surg. J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.mrrev.2016.07.010","article-title":"Ionizing radiation induced cataracts: Recent biological and mechanistic developments and perspectives for future research","volume":"770","author":"Ainsbury","year":"2016","journal-title":"Mutat. Res. Rev. Mutat. Res."},{"key":"ref_5","first-page":"92","article-title":"Lens epithelial cell proliferation in response to ionizing radiation","volume":"197","author":"Barnard","year":"2022","journal-title":"Radiat. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1080\/09553002.2018.1450535","article-title":"Radiosensitivity: A term with various meanings at the origin of numerous confusions. A semantic analysis","volume":"94","author":"Britel","year":"2018","journal-title":"Int. J. Radiat. Biol."},{"key":"ref_7","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_8","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1007\/s12551-015-0176-4","article-title":"Biophysical chemistry of the ageing eye lens","volume":"7","author":"Ray","year":"2015","journal-title":"Biophys. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1111\/cge.12182","article-title":"Genetics of human cataract","volume":"84","author":"Shiels","year":"2013","journal-title":"Clin. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1093\/rpd\/ncr299","article-title":"Radiation and cataract","volume":"147","author":"Rehani","year":"2011","journal-title":"Radiat. Prot. Dosim."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1016\/j.jvir.2016.11.043","article-title":"Radiation Cataractogenesis: The Progression of Our Understanding and Its Clinical Consequences","volume":"28","author":"Khan","year":"2017","journal-title":"J. Vasc. Interv. Radiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1080\/09553002.2022.2074166","article-title":"Individual response of the ocular lens to ionizing radiation","volume":"99","author":"Barnard","year":"2022","journal-title":"Int. J. Radiat. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1093\/jrr\/rru036","article-title":"Emerging issues in radiogenic cataracts and cardiovascular disease","volume":"55","author":"Hamada","year":"2014","journal-title":"J. Radiat. Res."},{"key":"ref_14","unstructured":"ICRP (1955). 1954 Recommendations of the International Commission on Radiological Protection. Br. J. Radiol., 28."},{"key":"ref_15","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_16","doi-asserted-by":"crossref","first-page":"1843","DOI":"10.1016\/j.ijcard.2012.04.124","article-title":"Interventional cardiologists and risk of radiation-induced cataract: Results of a French multicenter observational study","volume":"167","author":"Jacob","year":"2013","journal-title":"Int. J. Cardiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/ccd.27114","article-title":"Risk of cataract among interventional cardiologists and catheterization lab staff: A systematic review and meta-analysis","volume":"90","author":"Elmaraezy","year":"2017","journal-title":"Catheter. Cardiovasc. Interv."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"663","DOI":"10.13075\/ijomeh.1896.01456","article-title":"Occupational exposure to ionizing radiation and lens opacity in interventional cardiologists","volume":"32","author":"Piernik","year":"2019","journal-title":"Int. J. Occup. Med. Environ. Health"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1080\/09553002.2020.1812759","article-title":"Etiology of posterior subcapsular cataracts based on a review of risk factors including aging, diabetes, and ionizing radiation","volume":"96","author":"Richardson","year":"2020","journal-title":"Int. J. Radiat. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1667\/RR1688.1","article-title":"Radiation cataractogenesis: A review of recent studies","volume":"172","author":"Ainsbury","year":"2009","journal-title":"Radiat. Res."},{"key":"ref_21","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_22","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/j.ijrobp.2016.05.027","article-title":"The Henri Mondor Procedure of Morbidity and Mortality Review Meetings: Prospective Registration of Clinical, Dosimetric, and Individual Radiosensitivity Data of Patients With Severe Radiation Toxicity","volume":"96","author":"Belkacemi","year":"2016","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_23","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_24","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_25","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_26","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_27","doi-asserted-by":"crossref","unstructured":"Deneuve, S., Mirjolet, C., Bastogne, T., Duclos, M., Retif, P., Zrounba, P., Roux, P.E., Poupart, M., Vogin, G., and Foray, N. (2021). Proof of concept of a binary blood assay for predicting radiosensitivity. Cancers, 13.","DOI":"10.3390\/cancers13102477"},{"key":"ref_28","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_29","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_30","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":"2021","journal-title":"Mol. Neurobiol."},{"key":"ref_31","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_32","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_33","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_34","doi-asserted-by":"crossref","unstructured":"Berthel, E., Pujo-Menjouet, L., Le Reun, E., Sonzogni, L., Al-Choboq, J., Chekroun, A., Granzotto, A., Devic, C., Ferlazzo, M.L., and Pereira, S. (2023). Toward an early diagnosis for Alzheimer\u2019s disease based on the perinuclear localization of the ATM protein. Cells, 12.","DOI":"10.3390\/cells12131747"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Fujimichi, Y., and Hamada, N. (2014). Ionizing irradiation not only inactivates clonogenic potential in primary normal human diploid lens epithelial cells but also stimulates cell proliferation in a subset of this population. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0098154"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1111\/acel.12540","article-title":"Activated monocytes resist elimination by retinal pigment epithelium and downregulate their OTX2 expression via TNF-\u03b1","volume":"16","author":"Mathis","year":"2017","journal-title":"Aging Cell"},{"key":"ref_37","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_38","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_39","doi-asserted-by":"crossref","unstructured":"Ristic, M., Brockly, F., Piechaczyk, M., and Bossis, G. (2016). Detection of Protein\u2013Protein Interactions and Posttranslational Modifications Using the Proximity Ligation Assay: Application to the Study of the SUMO Pathway, Humana Press Inc.","DOI":"10.1007\/978-1-4939-3756-1_17"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.jtbi.2013.05.020","article-title":"A single formula to describe radiation-induced protein relocalization: Towards a mathematical definition of individual radiosensitivity","volume":"333","author":"Bodgi","year":"2013","journal-title":"J. Theor. Biol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Le Reun, E., Bodgi, L., Granzotto, A., Sonzogni, L., Ferlazzo, M.L., Al-Choboq, J., El-Nachef, L., Restier-Verlet, J., Berthel, E., and Devic, C. (2022). Quantitative Correlations between Radiosensitivity Biomarkers Show That the ATM Protein Kinase Is Strongly Involved in the Radiotoxicities Observed after Radiotherapy. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231810434"},{"key":"ref_42","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_43","doi-asserted-by":"crossref","unstructured":"El Nachef, L., Berthel, E., Ferlazzo, M.L., Le Reun, E., Al-Choboq, J., Restier-Verlet, J., Granzotto, A., Sonzogni, L., Bourguignon, M., and Foray, N. (2022). Cancer and Radiosensitivity Syndromes: Is Impaired Nuclear ATM Kinase Activity the Primum Movens?. Cancers, 14.","DOI":"10.3390\/cancers14246141"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.preteyeres.2006.10.003","article-title":"Crystallins in the eye: Function and pathology","volume":"26","author":"Andley","year":"2007","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"20190829","DOI":"10.1259\/bjr.20190829","article-title":"An update on effects of ionizing radiation exposure on the eye","volume":"93","author":"Hamada","year":"2020","journal-title":"Br. J. Radiol."},{"key":"ref_46","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_47","unstructured":"ICRP (2007). The 2007 Recommendations of the International Commission on Radiological Protection. ICRP publication 103. Ann. ICRP, 37, 1\u2013332."},{"key":"ref_48","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_49","doi-asserted-by":"crossref","first-page":"21","DOI":"10.3390\/radiation3010002","article-title":"Molecular and Cellular Responses to Ionization Radiation in Untransformed Fibroblasts from the Rothmund-Thomson Syndrome: Influence of the Nucleo-Shuttling of the ATM Protein Kinase","volume":"3","author":"Nehal","year":"2023","journal-title":"Radiation"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1559325820913784","DOI":"10.1177\/1559325820913784","article-title":"Influence of Individual Radiosensitivity on the Hormesis Phenomenon: Toward a Mechanistic Explanation Based on the Nucleoshuttling of ATM Protein","volume":"18","author":"Devic","year":"2020","journal-title":"Dose Response"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1559325818789836","DOI":"10.1177\/1559325818789836","article-title":"Influence of Individual Radiosensitivity on the Adaptive Response Phenomenon: Toward a Mechanistic Explanation Based on the Nucleo-Shuttling of ATM Protein","volume":"16","author":"Devic","year":"2018","journal-title":"Dose Response"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/16\/2118\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:38:43Z","timestamp":1760128723000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/16\/2118"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,21]]},"references-count":51,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2023,8]]}},"alternative-id":["cells12162118"],"URL":"https:\/\/doi.org\/10.3390\/cells12162118","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,21]]}}}