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Activation of efficient DNA repair mechanisms after photon and proton irradiation of human chondrosarcoma cells

Although particle therapy with protons has proven to be beneficial in the treatment of chondrosarcoma compared to photon-based (X-ray) radiation therapy, the cellular and molecular mechanisms have not yet been sufficiently investigated. Cell viability and colony forming ability were analyzed after X...

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Autores principales: Lohberger, Birgit, Glänzer, Dietmar, Eck, Nicole, Kerschbaum-Gruber, Sylvia, Mara, Elisabeth, Deycmar, Simon, Madl, Tobias, Kashofer, Karl, Georg, Petra, Leithner, Andreas, Georg, Dietmar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8677811/
https://www.ncbi.nlm.nih.gov/pubmed/34916568
http://dx.doi.org/10.1038/s41598-021-03529-9
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author Lohberger, Birgit
Glänzer, Dietmar
Eck, Nicole
Kerschbaum-Gruber, Sylvia
Mara, Elisabeth
Deycmar, Simon
Madl, Tobias
Kashofer, Karl
Georg, Petra
Leithner, Andreas
Georg, Dietmar
author_facet Lohberger, Birgit
Glänzer, Dietmar
Eck, Nicole
Kerschbaum-Gruber, Sylvia
Mara, Elisabeth
Deycmar, Simon
Madl, Tobias
Kashofer, Karl
Georg, Petra
Leithner, Andreas
Georg, Dietmar
author_sort Lohberger, Birgit
collection PubMed
description Although particle therapy with protons has proven to be beneficial in the treatment of chondrosarcoma compared to photon-based (X-ray) radiation therapy, the cellular and molecular mechanisms have not yet been sufficiently investigated. Cell viability and colony forming ability were analyzed after X-ray and proton irradiation (IR). Cell cycle was analyzed using flow cytometry and corresponding regulator genes and key players of the DNA repair mechanisms were measured using next generation sequencing, protein expression and immunofluorescence staining. Changes in metabolic phenotypes were determined with nuclear magnetic resonance spectroscopy. Both X-ray and proton IR resulted in reduced cell survival and a G2/M phase arrest of the cell cycle. Especially 1 h after IR, a significant dose-dependent increase of phosphorylated γH2AX foci was observed. This was accompanied with a reprogramming in cellular metabolism. Interestingly, within 24 h the majority of clearly visible DNA damages were repaired and the metabolic phenotype restored. Involved DNA repair mechanisms are, besides the homology directed repair (HDR) and the non-homologous end-joining (NHEJ), especially the mismatch mediated repair (MMR) pathway with the key players EXO1, MSH3, and PCNA. Chondrosarcoma cells regenerates the majority of DNA damages within 24 h. These molecular mechanisms represent an important basis for an improved therapy.
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spelling pubmed-86778112021-12-20 Activation of efficient DNA repair mechanisms after photon and proton irradiation of human chondrosarcoma cells Lohberger, Birgit Glänzer, Dietmar Eck, Nicole Kerschbaum-Gruber, Sylvia Mara, Elisabeth Deycmar, Simon Madl, Tobias Kashofer, Karl Georg, Petra Leithner, Andreas Georg, Dietmar Sci Rep Article Although particle therapy with protons has proven to be beneficial in the treatment of chondrosarcoma compared to photon-based (X-ray) radiation therapy, the cellular and molecular mechanisms have not yet been sufficiently investigated. Cell viability and colony forming ability were analyzed after X-ray and proton irradiation (IR). Cell cycle was analyzed using flow cytometry and corresponding regulator genes and key players of the DNA repair mechanisms were measured using next generation sequencing, protein expression and immunofluorescence staining. Changes in metabolic phenotypes were determined with nuclear magnetic resonance spectroscopy. Both X-ray and proton IR resulted in reduced cell survival and a G2/M phase arrest of the cell cycle. Especially 1 h after IR, a significant dose-dependent increase of phosphorylated γH2AX foci was observed. This was accompanied with a reprogramming in cellular metabolism. Interestingly, within 24 h the majority of clearly visible DNA damages were repaired and the metabolic phenotype restored. Involved DNA repair mechanisms are, besides the homology directed repair (HDR) and the non-homologous end-joining (NHEJ), especially the mismatch mediated repair (MMR) pathway with the key players EXO1, MSH3, and PCNA. Chondrosarcoma cells regenerates the majority of DNA damages within 24 h. These molecular mechanisms represent an important basis for an improved therapy. Nature Publishing Group UK 2021-12-16 /pmc/articles/PMC8677811/ /pubmed/34916568 http://dx.doi.org/10.1038/s41598-021-03529-9 Text en © The Author(s) 2021 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
Lohberger, Birgit
Glänzer, Dietmar
Eck, Nicole
Kerschbaum-Gruber, Sylvia
Mara, Elisabeth
Deycmar, Simon
Madl, Tobias
Kashofer, Karl
Georg, Petra
Leithner, Andreas
Georg, Dietmar
Activation of efficient DNA repair mechanisms after photon and proton irradiation of human chondrosarcoma cells
title Activation of efficient DNA repair mechanisms after photon and proton irradiation of human chondrosarcoma cells
title_full Activation of efficient DNA repair mechanisms after photon and proton irradiation of human chondrosarcoma cells
title_fullStr Activation of efficient DNA repair mechanisms after photon and proton irradiation of human chondrosarcoma cells
title_full_unstemmed Activation of efficient DNA repair mechanisms after photon and proton irradiation of human chondrosarcoma cells
title_short Activation of efficient DNA repair mechanisms after photon and proton irradiation of human chondrosarcoma cells
title_sort activation of efficient dna repair mechanisms after photon and proton irradiation of human chondrosarcoma cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8677811/
https://www.ncbi.nlm.nih.gov/pubmed/34916568
http://dx.doi.org/10.1038/s41598-021-03529-9
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