Cargando…

Impact of hypoxia on the double-strand break repair after photon and carbon ion irradiation of radioresistant HNSCC cells

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Wozny, Anne-Sophie, Alphonse, Gersende, Cassard, Audrey, Malésys, Céline, Louati, Safa, Beuve, Michael, Lalle, Philippe, Ardail, Dominique, Nakajima, Tetsuo, Rodriguez-Lafrasse, Claire
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7721800/
https://www.ncbi.nlm.nih.gov/pubmed/33288855
http://dx.doi.org/10.1038/s41598-020-78354-7
_version_ 1783620093404512256
author Wozny, Anne-Sophie
Alphonse, Gersende
Cassard, Audrey
Malésys, Céline
Louati, Safa
Beuve, Michael
Lalle, Philippe
Ardail, Dominique
Nakajima, Tetsuo
Rodriguez-Lafrasse, Claire
author_facet Wozny, Anne-Sophie
Alphonse, Gersende
Cassard, Audrey
Malésys, Céline
Louati, Safa
Beuve, Michael
Lalle, Philippe
Ardail, Dominique
Nakajima, Tetsuo
Rodriguez-Lafrasse, Claire
author_sort Wozny, Anne-Sophie
collection PubMed
description 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.
format Online
Article
Text
id pubmed-7721800
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-77218002020-12-09 Impact of hypoxia on the double-strand break repair after photon and carbon ion irradiation of radioresistant HNSCC cells Wozny, Anne-Sophie Alphonse, Gersende Cassard, Audrey Malésys, Céline Louati, Safa Beuve, Michael Lalle, Philippe Ardail, Dominique Nakajima, Tetsuo Rodriguez-Lafrasse, Claire Sci Rep Article 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. Nature Publishing Group UK 2020-12-07 /pmc/articles/PMC7721800/ /pubmed/33288855 http://dx.doi.org/10.1038/s41598-020-78354-7 Text en © The Author(s) 2020 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/.
spellingShingle Article
Wozny, Anne-Sophie
Alphonse, Gersende
Cassard, Audrey
Malésys, Céline
Louati, Safa
Beuve, Michael
Lalle, Philippe
Ardail, Dominique
Nakajima, Tetsuo
Rodriguez-Lafrasse, Claire
Impact of hypoxia on the double-strand break repair after photon and carbon ion irradiation of radioresistant HNSCC cells
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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7721800/
https://www.ncbi.nlm.nih.gov/pubmed/33288855
http://dx.doi.org/10.1038/s41598-020-78354-7
work_keys_str_mv AT woznyannesophie impactofhypoxiaonthedoublestrandbreakrepairafterphotonandcarbonionirradiationofradioresistanthnscccells
AT alphonsegersende impactofhypoxiaonthedoublestrandbreakrepairafterphotonandcarbonionirradiationofradioresistanthnscccells
AT cassardaudrey impactofhypoxiaonthedoublestrandbreakrepairafterphotonandcarbonionirradiationofradioresistanthnscccells
AT malesysceline impactofhypoxiaonthedoublestrandbreakrepairafterphotonandcarbonionirradiationofradioresistanthnscccells
AT louatisafa impactofhypoxiaonthedoublestrandbreakrepairafterphotonandcarbonionirradiationofradioresistanthnscccells
AT beuvemichael impactofhypoxiaonthedoublestrandbreakrepairafterphotonandcarbonionirradiationofradioresistanthnscccells
AT lallephilippe impactofhypoxiaonthedoublestrandbreakrepairafterphotonandcarbonionirradiationofradioresistanthnscccells
AT ardaildominique impactofhypoxiaonthedoublestrandbreakrepairafterphotonandcarbonionirradiationofradioresistanthnscccells
AT nakajimatetsuo impactofhypoxiaonthedoublestrandbreakrepairafterphotonandcarbonionirradiationofradioresistanthnscccells
AT rodriguezlafrasseclaire impactofhypoxiaonthedoublestrandbreakrepairafterphotonandcarbonionirradiationofradioresistanthnscccells