{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T01:09:58Z","timestamp":1790730598112,"version":"4.1.0"},"reference-count":75,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,3,13]],"date-time":"2023-03-13T00:00:00Z","timestamp":1678665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Commissariat General \u00e0 l\u2019Investissement (Programmes Investissement d\u2019Avenir (INDIRA Project))"},{"name":"Centre National d\u2019Etudes Spatiales (ICARE Project)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>The radiation protection strategy with chemical agents has long been based on an antioxidative approach consisting in reducing the number of radical oxygen and nitrogen species responsible for the formation of the radiation-induced (RI) DNA damage, notably the DNA double-strand breaks (DSB), whose subset participates in the RI lethal effect as unrepairable damage. Conversely, a DSB repair-stimulating strategy that may be called the \u201cpro-episkevic\u201d approach (from the ancient Greek episkeve, meaning repair) can be proposed. The pro-episkevic approach directly derives from a mechanistic model based on the RI nucleoshuttling of the ATM protein (RIANS) and contributes to increase the number of DSB managed by NHEJ, the most predominant DSB repair and signaling pathway in mammalians. Here, three radioresistant and three radiosensitive human fibroblast cell lines were pretreated with antioxidative agents (N-acetylcysteine or amifostine) or to two pro-episkevic agents (zoledronate or pravastatin or both (ZOPRA)) before X-ray irradiation. The fate of the RI DSB was analyzed by using \u03b3H2AX and pATM immunofluorescence. While amifostine pretreatment appeared to be the most efficient antioxidative process, ZOPRA shows the most powerful radiation protection, suggesting that the pro-episkevic strategy may be an alternative to the antioxidative one. Additional investigations are needed to develop some new drugs that may elicit both antioxidative and pro-episkevic properties and to quantify the radiation protection action of both types of drugs applied concomitantly.<\/jats:p>","DOI":"10.3390\/biom13030524","type":"journal-article","created":{"date-parts":[[2023,3,14]],"date-time":"2023-03-14T03:04:46Z","timestamp":1678763086000},"page":"524","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Molecular Influence of the ATM Protein in the Treatment of Human Cells with Different Radioprotective Drugs: Comparisons between Antioxidative and Pro-Episkevic Strategies"],"prefix":"10.3390","volume":"13","author":[{"given":"Juliette","family":"Restier-Verlet","sequence":"first","affiliation":[{"name":"INSERM U1296 Unit \u201cRadiation: Defense, Health, Environment\u201d, Centre L\u00e9on-B\u00e9rard, 69008 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Drouet","sequence":"additional","affiliation":[{"name":"INSERM U1296 Unit \u201cRadiation: Defense, Health, Environment\u201d, Centre L\u00e9on-B\u00e9rard, 69008 Lyon, France"},{"name":"Division D\u00e9fense NRBC, Institut de Recherche Biom\u00e9dicale des Arm\u00e9es, 91220 Br\u00e9tigny-sur-Orge, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pauline","family":"Pras","sequence":"additional","affiliation":[{"name":"INSERM U1296 Unit \u201cRadiation: Defense, Health, Environment\u201d, Centre L\u00e9on-B\u00e9rard, 69008 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e9lanie L.","family":"Ferlazzo","sequence":"additional","affiliation":[{"name":"INSERM U1296 Unit \u201cRadiation: Defense, Health, Environment\u201d, Centre L\u00e9on-B\u00e9rard, 69008 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adeline","family":"Granzotto","sequence":"additional","affiliation":[{"name":"INSERM U1296 Unit \u201cRadiation: Defense, Health, Environment\u201d, Centre L\u00e9on-B\u00e9rard, 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, Centre L\u00e9on-B\u00e9rard, 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 \u201cRadiation: Defense, Health, Environment\u201d, Centre L\u00e9on-B\u00e9rard, 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, Centre L\u00e9on-B\u00e9rard, 69008 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Fran\u00e7ois","sequence":"additional","affiliation":[{"name":"INSERM U1296 Unit \u201cRadiation: Defense, Health, Environment\u201d, Centre L\u00e9on-B\u00e9rard, 69008 Lyon, France"},{"name":"Division D\u00e9fense NRBC, Institut de Recherche Biom\u00e9dicale des Arm\u00e9es, 91220 Br\u00e9tigny-sur-Orge, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Bourguignon","sequence":"additional","affiliation":[{"name":"INSERM U1296 Unit \u201cRadiation: Defense, Health, Environment\u201d, Centre L\u00e9on-B\u00e9rard, 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, Centre L\u00e9on-B\u00e9rard, 69008 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,13]]},"reference":[{"key":"ref_1","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. 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