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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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
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. |
format | Online Article Text |
id | pubmed-8677811 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
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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