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...

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Bibliographic Details
Published in:	Scientific reports Vol. 10; no. 1; p. 21357
Main Authors:	Wozny, Anne-Sophie, Alphonse, Gersende, Cassard, Audrey, Malésys, Céline, Louati, Safa, Beuve, Michael, Lalle, Philippe, Ardail, Dominique, Nakajima, Tetsuo, Rodriguez-Lafrasse, Claire
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 07-12-2020 Nature Publishing Group Nature Portfolio
Subjects:	631/67/1536 631/67/327 631/67/71 Cell Cycle - genetics Cell Cycle - radiation effects Cell Hypoxia - genetics Cell Hypoxia - physiology Cell Line, Tumor Cyclin-Dependent Kinase Inhibitor p16 - genetics Deoxyribonucleic acid DNA DNA Breaks, Double-Stranded - radiation effects DNA damage DNA repair DNA-dependent protein kinase Double-strand break repair Fluorescent Antibody Technique Genotype Head & neck cancer Heavy Ion Radiotherapy Homologous recombination Humanities and Social Sciences Humans Hypoxia Ions Irradiation multidisciplinary Neoplastic Stem Cells - metabolism Neoplastic Stem Cells - radiation effects Non-homologous end joining Photons Physics Radiation Radioresistance Science Science (multidisciplinary) Signal transduction Squamous cell carcinoma Squamous Cell Carcinoma of Head and Neck - genetics Squamous Cell Carcinoma of Head and Neck - radiotherapy Stem cells Tumor Microenvironment - genetics Tumor Microenvironment - radiation effects Tumor Suppressor Protein p53 - genetics X-Rays Yeast
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 PMCID: PMC7721800
ISSN:	2045-2322 2045-2322
DOI:	10.1038/s41598-020-78354-7