Abstract
Purpose
Even though X-ray beams are widely used in medical diagnosis or radiotherapy, the comparisons of their dose rates are scarce. We have recently demonstrated in vitro (clonogenic assay, cell viability, cell cycle, senescence) and in vivo (weight follow-up of animals and bordering epithelium staining of lesion), that for a single dose of irradiation, the relative biological effectiveness (RBE) deviates from 1 (up to twofold greater severe damage at the highest dose rate depending on the assay) when increasing the dose rate of high energy X-ray beams.
Material and methods
To further investigate the impact of the dose rate on RBE, in this study, we performed in vitro fractionated irradiations by using the same two dose rates (0.63 and 2.5 Gy.min−1) of high-energy X-rays (both at 4 MV) on normal endothelial cells (HUVECs). We investigated the viability/mortality, characterized radiation-induced senescence by using flow cytometry and measured gene analysis deregulations on custom arrays.
Results
The overall results enlighten that, in fractionated irradiations when varying the dose rate of high-energy X-rays, the RBE of photons deviates from 1 (up to 2.86 for viability/mortality experiments performed 21 days postirradiation).
Conclusion
These results strengthen the interest of multiparametric analysis approaches in providing an accurate evaluation of the outcomes of irradiated cells in support of clonogenic assays, especially when such assays are not feasible.
Acknowledgements
The authors would like to thank M. Razanajatovo and Y. Ristic for their help with irradiation on the Elekta Synergy Platform. This work was supported by Electricité de France EDF (Groupe Gestion Projet Radioprotection) and is included in the IRSN program ROSIRIS. This work was also supported by the “Cancéropole d’Ile de France” and “INCA Institut National du Cancer” (INCa 2018‐1‐PL BIO‐06). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Author contributions
M.B.K., M.D.S., V.B., G.T. and V.P.: Acquisition, analyses and interpretation of data. M.A.B.: statistical analyses, help in writing the manuscript. B.L.G, A.F, O.G. and F.M.: Critical review of the manuscript. V.P.: Writing the manuscript. V.P. and F.M.: Conception, design and supervising the project.
Disclosure statement
The authors have read the journal’s policy and have no competing interests. B.L.G. is employee at Electricité de France, Cap Ampère, Saint-Denis, France.
Additional information
Funding
Notes on contributors
Mariam Ben Kacem
Mariam Ben Kacem was a PhD student in radiobiology at the IRSN (2017–2020). Ben Kacem focused her work on studying the biological effects induced by different modalities of radiations both in vitro and in vivo.
Mohamed A. Benadjaoud
Mohamed Amine Benadjaoud is a researcher at the IRSN. Having a PhD in Biostatistics and a MSc in Medical Physics, his main activities include, through radiobiological data integration, the development of multiscale risk models.
Morgane Dos Santos
Morgane Dos Santos is a physics researcher in charge of the SARRP (Small Animal Radiation Research Platform) platform at the IRSN. Her work is also focused on the design and implementation of dosimetry protocols.
Valérie Buard
Valérie Buard is a research technician Laboratory of MEDical Radiobiology (LRMed) at IRSN. Buard mainly works on cell culture, immunohistochemistry and conventional/confocal imaging.
Georges Tarlet
Georges Tarlet is a research technician Laboratory of MEDical Radiobiology (LRMed) at IRSN. Tarlet mainly works on molecular biology, cloning and proteomics.
Bernard Le Guen
Bernard Le Guen is the Vice-President for international affairs (nuclear) at Electricité de France. Le Guen is the actual President of the Executive Council of IRPA (International Radiation Protection Association).
A. François
Agnès François is a researcher radiobiologist at the IRSN. She is an expert of radiation-induced normal tissue damages.
O Guipaud
Olivier Guipaud is a researcher radiobiologist at the IRSN, more particularly in the field of the vascular endothelium. Guipaud focuses his work on endothelial factors, following a radiotherapy, which are involved in the recruitment of immune cells both into tumors and normal tissues.
F Milliat
Fabien Milliat is a researcher radiobiologist and the head of the Laboratory of MEDical Radiobiology (LRMed) at the IRSN. Milliat is an expert on the role of the vascular compartment in radiation-induced normal tissue damages.
Vincent Paget
Vincent Paget is a researcher radiobiologist at IRSN who focus his work on the development of methods aiming at improving the prediction of adverse effects on healthy tissues exposed to different modalities of ionizing radiations.