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dc.contributor.authorLópez Nieva, María Pilar 
dc.contributor.authorGonzález Vasconcellos, Iria
dc.contributor.authorGonzález Sánchez, Laura
dc.contributor.authorCobos Fernández, María Ángeles 
dc.contributor.authorRuiz García, Sara
dc.contributor.authorSánchez Pérez, Raúl
dc.contributor.authorAroca Peinado, Ángel 
dc.contributor.authorFernández Piqueras, José 
dc.contributor.authorSantos Hernández, Fco. Javier 
dc.contributor.otherUAM. Departamento de Biologíaes_ES
dc.date.accessioned2022-09-27T09:45:42Z
dc.date.available2022-09-27T09:45:42Z
dc.date.issued2022-02-24
dc.identifier.citationScientific Reports 12.1 (2022): 3144es_ES
dc.identifier.issn2045-2322es_ES
dc.identifier.urihttp://hdl.handle.net/10486/704289
dc.description.abstractIn the quest for more effective radiation treatment options that can improve both cell killing and healthy tissue recovery, combined radiation therapies are lately in the spotlight. The molecular response to a combined radiation regime where exposure to an initial low dose (priming dose) of ionizing radiation is administered prior to a subsequent higher radiation dose (challenging dose) after a given latency period have not been thoroughly explored. In this study we report on the differential response to either a combined radiation regime or a single challenging dose both in mouse in vivo and in human ex vivo thymocytes. A differential cell cycle response including an increase in the subG1 fraction on cells exposed to the combined regime was found. Together with this, a differential protein expression profiling in several pathways including cell cycle control (ATM, TP53, p21CDKN1A), damage response (γH2AX) and cell death pathways such as apoptosis (Cleaved Caspase-3, PARP1, PKCδ and H3T45ph) and ferroptosis (xCT/GPX4) was demonstrated. This study also shows the epigenetic regulation following a combined regime that alters the expression of chromatin modifiers such as DNMTs (DNMT1, DNMT2, DNMT3A, DNMT3B, DNMT3L) and glycosylases (MBD4 and TDG). Furthermore, a study of the underlying cellular status six hours after the priming dose alone showed evidence of retained modifications on the molecular and epigenetic pathways suggesting that the priming dose infers a “radiation awareness phenotype” to the thymocytes, a sensitization key to the differential response seen after the second hit with the challenging dose. These data suggest that combined-dose radiation regimes could be more efficient at making cells respond to radiation and it would be interesting to further investigate how can these schemes be of use to potential new radiation therapieses_ES
dc.format.extent12 pag.es_ES
dc.format.mimetypeapplication/pdfes_ES
dc.language.isoenges_ES
dc.publisherNature Researches_ES
dc.relation.ispartofScientific Reportses_ES
dc.rights© The Author(s) 2022es_ES
dc.subject.otherDNA damagees_ES
dc.subject.otherEpigenetic regulationes_ES
dc.subject.otherCell cyclees_ES
dc.subject.otherThymocytees_ES
dc.subject.otherGene expression regulationes_ES
dc.titleDifferential molecular response in mice and human thymocytes exposed to a combined-dose radiation regimees_ES
dc.typearticlees_ES
dc.subject.ecienciaBiología y Biomedicina / Biologíaes_ES
dc.relation.publisherversionhttps://doi.org/10.1038/s41598-022-07166-8es_ES
dc.identifier.doi10.1038/s41598-022-07166-8es_ES
dc.identifier.publicationfirstpage1es_ES
dc.identifier.publicationissue1es_ES
dc.identifier.publicationlastpage12es_ES
dc.identifier.publicationvolume12es_ES
dc.relation.projectIDGobierno de España. SAF2015-70561-Res_ES
dc.relation.projectIDComunidad de Madrid. 2017/BMD-3778/LINFOMASes_ES
dc.type.versioninfo:eu-repo/semantics/publishedVersiones_ES
dc.rights.ccReconocimientoes_ES
dc.rights.accessRightsopenAccesses_ES
dc.facultadUAMFacultad de Cienciases_ES
dc.facultadUAMFacultad de Medicinaes_ES
dc.institutoUAMCentro de Biología Molecular Severo Ochoa (CBMSO)es_ES


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