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

Autor(es):Mostrar menos -

Tang, Nicolas ^[1] ; Bueno, Marta ^[1] ; Meylan, Sylvain ^[2] ; Perrot, Yann ^[1] ; Tran, Hoang N. ^[1] ; Freneau, Amelie ^[1] ; Dos Santos, Morgane ^[1] ; Vaurijoux, Aurelie ^[1] ; Gruel, Gaetan ^[1] ; Bernal, Mario A. ^[3] ; Bordage, Marie-Claude ^{[4, 5]} ; Emfietzoglou, Dimitris ^[6] ; Francis, Ziad ^[7] ; Guatelli, Susanna ^[8] ; Ivanchenko, Vladimir ^{[9, 10]} ; Karamitros, Mathieu ^[11] ; Kyriakou, Ioanna ; Shin, Wook-Geun ^[11] ; Incerti, Sebastien ^{[11, 12]} ; Villagrasa, Carmen ^[1]

Afiliação do(s) autor(es):Mostrar menos -

^[1] IRSN, BP17, F-92262 Fontenay Aux Roses - France

^[2] SymAlgo Technol, 75 Rue Leon Frot, F-75011 Paris - France

^[3] Univ Estadual Campinas, Inst Fis Gleb Wataghin, BR-13083859 Campinas, SP - Brazil

^[4] Univ Paul Sabatier, INSERM, UMR 1037, CRCT, F-31330 Toulouse - France

^[5] Univ Toulouse III Paul Sabatier, UMR 1037, CRCT, F-31330 Toulouse - France

^[6] Univ Ioannina, Sch Med, Med Phys Lab, GR-45110 Ioannina - Greece

^[7] Univ St Joseph, Dept Phys, Beirut 11042020 - Lebanon

^[8] Univ Wollongong, Ctr Med Radiat Phys, Wollongong, NSW 2522 - Australia

^[9] Geant4 Associates Int Ltd, Hebden Bridge HX7 7BT - England

^[10] Tomsk State Univ, LEPHE, Tomsk 634050 - Russia

^[11] Univ Bordeaux, CNRS, IN2P3, Ctr Nucl Bordeaux Gradignan, CENBG, Chemin Solarium, BP120, F-33175 Gradignan - France

^[12] CENBG, IN2P3, CNRS, Chemin Solarium, BP120, F-33175 Gradignan - France

• Tipo de documento: Artigo Científico
• Fonte: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 20, n. 24 DEC 2019.
• Citações Web of Science: 0

Resumo

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 (10(9)) base pair (Gbp) and DSB complexity was derived in order to be compared to experimental data expressed as numbers of histone variant H2AX (gamma-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 surete nucleaire) 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. (AU)

• Processo FAPESP: 11/51594-2 - Desenvolvimento de um sistema computacional para a simulação da interação da radiação ionizante com o material genético humano
• Beneficiário: Mario Antonio Bernal Rodriguez
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 18/15316-7 - Estudo da interação de partículas carregadas pesadas com o DNA usando métodos computacionais
• Beneficiário: Mario Antonio Bernal Rodriguez
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores - Fase 2
• Processo FAPESP: 15/21873-8 - Desenvolvimento e implementação de metodologias para otimização de técnicas de imagens em radiologia digital
• Beneficiário: Alessandra Tomal
• Modalidade de apoio: Auxílio à Pesquisa - Regular