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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Autores principales:	Anne-Sophie Wozny, Gersende Alphonse, Audrey Cassard, Céline Malésys, Safa Louati, Michael Beuve, Philippe Lalle, Dominique Ardail, Tetsuo Nakajima, Claire Rodriguez-Lafrasse
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b9246a0bfb4742b4a947afac465121a4
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spelling	oai:doaj.org-article:b9246a0bfb4742b4a947afac465121a42021-12-02T11:40:41ZImpact of hypoxia on the double-strand break repair after photon and carbon ion irradiation of radioresistant HNSCC cells10.1038/s41598-020-78354-72045-2322https://doaj.org/article/b9246a0bfb4742b4a947afac465121a42020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-78354-7https://doaj.org/toc/2045-2322Abstract 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.Anne-Sophie WoznyGersende AlphonseAudrey CassardCéline MalésysSafa LouatiMichael BeuvePhilippe LalleDominique ArdailTetsuo NakajimaClaire Rodriguez-LafrasseNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-18 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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
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.
format	article
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
title	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_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_sort	impact of hypoxia on the double-strand break repair after photon and carbon ion irradiation of radioresistant hnscc cells
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/b9246a0bfb4742b4a947afac465121a4
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Impact of hypoxia on the double-strand break repair after photon and carbon ion irradiation of radioresistant HNSCC cells

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