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Differential molecular response in mice and human thymocytes exposed to a combined-dose radiation regime

In 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...

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Autores principales: López-Nieva, Pilar, González-Vasconcellos, Iria, González-Sánchez, Laura, Cobos-Fernández, María A., Ruiz-García, Sara, Sánchez Pérez, Raúl, Aroca, Ángel, Fernández-Piqueras, José, Santos, Javier
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8873405/
https://www.ncbi.nlm.nih.gov/pubmed/35210498
http://dx.doi.org/10.1038/s41598-022-07166-8
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author López-Nieva, Pilar
González-Vasconcellos, Iria
González-Sánchez, Laura
Cobos-Fernández, María A.
Ruiz-García, Sara
Sánchez Pérez, Raúl
Aroca, Ángel
Fernández-Piqueras, José
Santos, Javier
author_facet López-Nieva, Pilar
González-Vasconcellos, Iria
González-Sánchez, Laura
Cobos-Fernández, María A.
Ruiz-García, Sara
Sánchez Pérez, Raúl
Aroca, Ángel
Fernández-Piqueras, José
Santos, Javier
author_sort López-Nieva, Pilar
collection PubMed
description In 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, p21(CDKN1A)), 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 therapies.
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spelling pubmed-88734052022-02-25 Differential molecular response in mice and human thymocytes exposed to a combined-dose radiation regime López-Nieva, Pilar González-Vasconcellos, Iria González-Sánchez, Laura Cobos-Fernández, María A. Ruiz-García, Sara Sánchez Pérez, Raúl Aroca, Ángel Fernández-Piqueras, José Santos, Javier Sci Rep Article In 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, p21(CDKN1A)), 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 therapies. Nature Publishing Group UK 2022-02-24 /pmc/articles/PMC8873405/ /pubmed/35210498 http://dx.doi.org/10.1038/s41598-022-07166-8 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
López-Nieva, Pilar
González-Vasconcellos, Iria
González-Sánchez, Laura
Cobos-Fernández, María A.
Ruiz-García, Sara
Sánchez Pérez, Raúl
Aroca, Ángel
Fernández-Piqueras, José
Santos, Javier
Differential molecular response in mice and human thymocytes exposed to a combined-dose radiation regime
title Differential molecular response in mice and human thymocytes exposed to a combined-dose radiation regime
title_full Differential molecular response in mice and human thymocytes exposed to a combined-dose radiation regime
title_fullStr Differential molecular response in mice and human thymocytes exposed to a combined-dose radiation regime
title_full_unstemmed Differential molecular response in mice and human thymocytes exposed to a combined-dose radiation regime
title_short Differential molecular response in mice and human thymocytes exposed to a combined-dose radiation regime
title_sort differential molecular response in mice and human thymocytes exposed to a combined-dose radiation regime
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8873405/
https://www.ncbi.nlm.nih.gov/pubmed/35210498
http://dx.doi.org/10.1038/s41598-022-07166-8
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