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Open AccessArticle

Assessment of Radio-Induced Damage in Endothelial Cells Irradiated with 40 kVp, 220 kVp, and 4 MV X-rays by Means of Micro and Nanodosimetric Calculations

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IRSN, Institut de Radioprotection et de Sûreté Nucléaire, BP17, 92262 Fontenay aux Roses, France
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SymAlgo Technologies, 75 rue Léon Frot, 75011 Paris, France
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Instituto de Fisica Gleb Wataghin, Universidade Estadual de Campinas, Campinas 13083-859, SP, Brazil
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INSERM, Université Paul Sabatier, UMR 1037, CRCT, 31330 Toulouse, France
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Université Toulouse III-Paul Sabatier, UMR 1037, CRCT, 31330 Toulouse, France
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Medical Physics Laboratory, University of Ioannina, Medical School, GR-45110 Ioannina, Greece
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Department of Physics, Faculty of Sciences, Université Saint Joseph, 1104 2020 Beirut, Lebanon
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Centre for Medical Radiation Physics, University of Wollongong, 2522 Wollongong, Australia
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Geant4 Associates International Ltd., Hebden Bridge HX7 7BT, UK
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LEPHE, Tomsk State University, 634050 Tomsk, Russia
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Université de Bordeaux, CNRS/IN2P3, Centre Nucléaires de Bordeaux Gradignan, CENBG, chemin du solarium, BP120, 33175 Gradignan, France
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CNRS/IN2P3, Centre d’Etudes Nucléaires de Bordeaux Gradignan, CENBG, chemin du solarium, BP120, 33175 Gradignan, France
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Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(24), 6204; https://doi.org/10.3390/ijms20246204
Received: 28 October 2019 / Revised: 29 November 2019 / Accepted: 4 December 2019 / Published: 9 December 2019
(This article belongs to the Special Issue Radiation Damage in Biomolecules and Cells)
The objective of this work was to study the differences in terms of early biological effects that might exist between different X-rays energies by using a mechanistic approach. To this end, radiobiological experiments exposing cell monolayers to three X-ray energies were performed in order to assess the yields of early DNA damage, in particular of double-strand breaks (DSBs). The simulation of these irradiations was set in order to understand the differences in the obtained experimental results. Hence, simulated results in terms of microdosimetric spectra and early DSB induction were analyzed and compared to the experimental data. Human umbilical vein endothelial cells (HUVECs) were irradiated with 40, 220 kVp, and 4 MV X-rays. The Geant4 Monte Carlo simulation toolkit and its extension Geant4-DNA were used for the simulations. Microdosimetric calculations aiming to determine possible differences in the variability of the energy absorbed by the irradiated cell population for those photon spectra were performed on 10,000 endothelial cell nuclei representing a cell monolayer. Nanodosimetric simulations were also carried out using a computation chain that allowed the simulation of physical, physico-chemical, and chemical stages on a single realistic endothelial cell nucleus model including both heterochromatin and euchromatin. DNA damage was scored in terms of yields of prompt DSBs per Gray (Gy) and per giga (109) base pair (Gbp) and DSB complexity was derived in order to be compared to experimental data expressed as numbers of histone variant H2AX (γ-H2AX) foci per cell. The calculated microdosimetric spread in the irradiated cell population was similar when comparing between 40 and 220 kVp X-rays and higher when comparing with 4 MV X-rays. Simulated yields of induced DSB/Gy/Gbp were found to be equivalent to those for 40 and 220 kVp but larger than those for 4 MV, resulting in a relative biological effectiveness (RBE) of 1.3. Additionally, DSB complexity was similar between the considered photon spectra. Simulated results were in good agreement with experimental data obtained by IRSN (Institut de radioprotection et de sûreté nucléaire) radiobiologists. Despite differences in photon energy, few differences were observed when comparing between 40 and 220 kVp X-rays in microdosimetric and nanodosimetric calculations. Nevertheless, variations were observed when comparing between 40/220 kVp and 4 MV X-rays. Thanks to the simulation results, these variations were able to be explained by the differences in the production of secondary electrons with energies below 10 keV. View Full-Text
Keywords: Monte Carlo simulation; Geant4/Geant4-DNA; X-rays; microdosimetry; nanodosimetry; DSB yield Monte Carlo simulation; Geant4/Geant4-DNA; X-rays; microdosimetry; nanodosimetry; DSB yield
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Tang, N.; Bueno, M.; Meylan, S.; Perrot, Y.; Tran, H.N.; Freneau, A.; Dos Santos, M.; Vaurijoux, A.; Gruel, G.; Bernal, M.A.; Bordage, M.-C.; Emfietzoglou, D.; Francis, Z.; Guatelli, S.; Ivanchenko, V.; Karamitros, M.; Kyriakou, I.; Shin, W.-G.; Incerti, S.; Villagrasa, C. Assessment of Radio-Induced Damage in Endothelial Cells Irradiated with 40 kVp, 220 kVp, and 4 MV X-rays by Means of Micro and Nanodosimetric Calculations. Int. J. Mol. Sci. 2019, 20, 6204.

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