Impact of hypoxia on the double-strand break repair after photon and carbon ion irradiation of radioresistant HNSCC cells
Abstract DNA double-strand breaks (DSBs) induced by photon irradiation are the most deleterious damage for cancer cells and their efficient repair may contribute to radioresistance, particularly in hypoxic conditions. Carbon ions (C-ions) act independently of the oxygen concentration and trigger com...
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| Format: | Article |
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Nature Portfolio
2020-12-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-020-78354-7 |
| _version_ | 1818842501474156544 |
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| author | Anne-Sophie Wozny Gersende Alphonse Audrey Cassard Céline Malésys Safa Louati Michael Beuve Philippe Lalle Dominique Ardail Tetsuo Nakajima Claire Rodriguez-Lafrasse |
| author_facet | Anne-Sophie Wozny Gersende Alphonse Audrey Cassard Céline Malésys Safa Louati Michael Beuve Philippe Lalle Dominique Ardail Tetsuo Nakajima Claire Rodriguez-Lafrasse |
| author_sort | Anne-Sophie Wozny |
| collection | DOAJ |
| description | Abstract DNA double-strand breaks (DSBs) induced by photon irradiation are the most deleterious damage for cancer cells and their efficient repair may contribute to radioresistance, particularly in hypoxic conditions. Carbon ions (C-ions) act independently of the oxygen concentration and trigger complex- and clustered-DSBs difficult to repair. Understanding the interrelation between hypoxia, radiation-type, and DNA-repair is therefore essential for overcoming radioresistance. The DSBs signaling and the contribution of the canonical non-homologous end-joining (NHEJ-c) and homologous-recombination (HR) repair pathways were assessed by immunostaining in two cancer-stem-cell (CSCs) and non-CSCs HNSCC cell lines. Detection and signaling of DSBs were lower in response to C-ions than photons. Hypoxia increased the decay-rate of the detected DSBs (γH2AX) in CSCs after photons and the initiation of DSB repair signaling (P-ATM) in CSCs and non-CSCs after both radiations, but not the choice of DSB repair pathway (53BP1). Additionally, hypoxia increased the NHEJ-c (DNA-PK) and the HR pathway (RAD51) activation only after photons. Furthermore, the involvement of the HR seemed to be higher in CSCs after photons and in non-CSCs after C-ions. Taken together, our results show that C-ions may overcome the radioresistance of HNSCC associated with DNA repair, particularly in CSCs, and independently of a hypoxic microenvironment. |
| first_indexed | 2024-12-19T04:42:59Z |
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| id | doaj.art-b9246a0bfb4742b4a947afac465121a4 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-19T04:42:59Z |
| publishDate | 2020-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-b9246a0bfb4742b4a947afac465121a42022-12-21T20:35:34ZengNature PortfolioScientific Reports2045-23222020-12-0110111810.1038/s41598-020-78354-7Impact of hypoxia on the double-strand break repair after photon and carbon ion irradiation of radioresistant HNSCC cellsAnne-Sophie Wozny0Gersende Alphonse1Audrey Cassard2Céline Malésys3Safa Louati4Michael Beuve5Philippe Lalle6Dominique Ardail7Tetsuo Nakajima8Claire Rodriguez-Lafrasse9UMR CNRS5822/IN2P3, IP2I, PRISME, Laboratoire de Radiobiologie Cellulaire et Moléculaire, Faculté de Médecine Lyon-Sud, Univ Lyon, Université LyonUMR CNRS5822/IN2P3, IP2I, PRISME, Laboratoire de Radiobiologie Cellulaire et Moléculaire, Faculté de Médecine Lyon-Sud, Univ Lyon, Université LyonUMR CNRS5822/IN2P3, IP2I, PRISME, Laboratoire de Radiobiologie Cellulaire et Moléculaire, Faculté de Médecine Lyon-Sud, Univ Lyon, Université LyonUMR CNRS5822/IN2P3, IP2I, PRISME, Laboratoire de Radiobiologie Cellulaire et Moléculaire, Faculté de Médecine Lyon-Sud, Univ Lyon, Université LyonUMR CNRS5822/IN2P3, IP2I, PRISME, Laboratoire de Radiobiologie Cellulaire et Moléculaire, Faculté de Médecine Lyon-Sud, Univ Lyon, Université LyonUMR CNRS5822 /IN2P3, IP2I, PRISME, Univ Lyon, Université Lyon 1UMR CNRS5822/IN2P3, IP2I, PRISME, Laboratoire de Radiobiologie Cellulaire et Moléculaire, Faculté de Médecine Lyon-Sud, Univ Lyon, Université LyonUMR CNRS5822/IN2P3, IP2I, PRISME, Laboratoire de Radiobiologie Cellulaire et Moléculaire, Faculté de Médecine Lyon-Sud, Univ Lyon, Université LyonDepartment of Radiation Effects Research, National Institute of Radiological Sciences, National Institute for Quantum and Radiological Science and TechnologyUMR CNRS5822/IN2P3, IP2I, PRISME, Laboratoire de Radiobiologie Cellulaire et Moléculaire, Faculté de Médecine Lyon-Sud, Univ Lyon, Université LyonAbstract DNA double-strand breaks (DSBs) induced by photon irradiation are the most deleterious damage for cancer cells and their efficient repair may contribute to radioresistance, particularly in hypoxic conditions. Carbon ions (C-ions) act independently of the oxygen concentration and trigger complex- and clustered-DSBs difficult to repair. Understanding the interrelation between hypoxia, radiation-type, and DNA-repair is therefore essential for overcoming radioresistance. The DSBs signaling and the contribution of the canonical non-homologous end-joining (NHEJ-c) and homologous-recombination (HR) repair pathways were assessed by immunostaining in two cancer-stem-cell (CSCs) and non-CSCs HNSCC cell lines. Detection and signaling of DSBs were lower in response to C-ions than photons. Hypoxia increased the decay-rate of the detected DSBs (γH2AX) in CSCs after photons and the initiation of DSB repair signaling (P-ATM) in CSCs and non-CSCs after both radiations, but not the choice of DSB repair pathway (53BP1). Additionally, hypoxia increased the NHEJ-c (DNA-PK) and the HR pathway (RAD51) activation only after photons. Furthermore, the involvement of the HR seemed to be higher in CSCs after photons and in non-CSCs after C-ions. Taken together, our results show that C-ions may overcome the radioresistance of HNSCC associated with DNA repair, particularly in CSCs, and independently of a hypoxic microenvironment.https://doi.org/10.1038/s41598-020-78354-7 |
| spellingShingle | Anne-Sophie Wozny Gersende Alphonse Audrey Cassard Céline Malésys Safa Louati Michael Beuve Philippe Lalle Dominique Ardail Tetsuo Nakajima Claire Rodriguez-Lafrasse Impact of hypoxia on the double-strand break repair after photon and carbon ion irradiation of radioresistant HNSCC cells Scientific Reports |
| title | Impact of hypoxia on the double-strand break repair after photon and carbon ion irradiation of radioresistant HNSCC cells |
| title_full | Impact of hypoxia on the double-strand break repair after photon and carbon ion irradiation of radioresistant HNSCC cells |
| title_fullStr | Impact of hypoxia on the double-strand break repair after photon and carbon ion irradiation of radioresistant HNSCC cells |
| title_full_unstemmed | Impact of hypoxia on the double-strand break repair after photon and carbon ion irradiation of radioresistant HNSCC cells |
| title_short | Impact of hypoxia on the double-strand break repair after photon and carbon ion irradiation of radioresistant HNSCC cells |
| title_sort | impact of hypoxia on the double strand break repair after photon and carbon ion irradiation of radioresistant hnscc cells |
| url | https://doi.org/10.1038/s41598-020-78354-7 |
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