Influence of chromatin compaction on simulated early radiation‐induced <scp>DNA</scp> damage using Geant4‐<scp>DNA</scp>

Tang, Nicolas; Bueno, M.; Meylan, Sylvain; Incerti, S.; Tran, H.N.; Vaurijoux, Aurélie; Gruel, Gaëtan; Villagrasa, C.

doi:10.1002/mp.13405

Cited by 44 publications

(66 citation statements)

References 39 publications

(132 reference statements)

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“…It should be noted that the scoring method for DNA damage can strongly influence the final yield of simulated DSB induction. As mentioned in our previous works [35,46,47], a change in the parameters to score direct and/or indirect strand breaks can greatly increase the yield of DSB. Moreover, a chemical simulation end-time of 10 ns has been suggested in our computation chain instead of the 2.5 ns currently used when considering the cell nucleus model filled with heterochromatin and euchromatin [46].…”

Section: Discussionmentioning

confidence: 91%

“…As mentioned in our previous works [35,46,47], a change in the parameters to score direct and/or indirect strand breaks can greatly increase the yield of DSB. Moreover, a chemical simulation end-time of 10 ns has been suggested in our computation chain instead of the 2.5 ns currently used when considering the cell nucleus model filled with heterochromatin and euchromatin [46]. Hence, simulations were also performed with a parameter of 10 ns and the number of DSBs showed an increase by a factor of~1.3 with respect to those obtained with 2.5 ns ( Table 2).…”

Section: Discussionmentioning

confidence: 91%

“…Then, the number of simulated DSBs was correlated with measurements of γ-H2AX foci. For these calculations, a model representing an endothelial cell nucleus filled with around 6 Gbp [44] of DNA composed of heterochromatin and euchromatin in the Gap0/Gap1 (G0/G1) phase of the cell cycle was generated with DnaFabric [45,46] software and used in the simulation.…”

Section: Introductionmentioning

confidence: 99%

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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

Tang

Bueno

Meylan³

et al. 2019

IJMS

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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.

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Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

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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

Tang

Bueno

Meylan³

et al. 2019

IJMS

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“…Such researches would improve the realism of our damage estimations to allow comparisons to other MC simulation results or biological data. Geant4‐DNA can already be used to study the production and transportation of chemical species, although only in liquid water . It will be interesting to perform simulations of the physico‐chemical and chemical stages of radiation in detailed DNA geometries when the processes will be available for the public in Geant4 .…”

Section: Discussionmentioning

confidence: 99%

Minibeam radiation therapy: A micro‐ and nano‐dosimetry Monte Carlo study

et al. 2020

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Purpose Minibeam radiation therapy (MBRT) is an innovative strategy based on a distinct dose delivery method that is administered using a series of narrow (submillimetric) parallel beams. To shed light on the biological effects of MBRT irradiation, we explored the micro‐ and nanodosimetric characteristics of three promising MBRT modalities (photon, electron, and proton) using Monte Carlo (MC) calculations. Methods Irradiation with proton (100 MeV), electron (300 MeV), and photon (effective energy of 69 keV) minibeams were simulated using Geant4 MC code and the Geant4‐DNA extension, which allows the simulation of energy transfer points with nanometric accuracy. As the target of the simulations, cells containing spherical nuclei with or without a detailed description of the DNA (deoxyribonucleic acid) geometry were placed at different depths in peak and valley regions in a water phantom. The energy deposition and number of events in the cell nuclei were recorded in the microdosimetry study, and the number of DNA breaks and their complexity were determined in the nanodosimetric study, where a multi‐scale simulation approach was used for the latter. For DNA damage assessment, an adapted DBSCAN clustering algorithm was used. To compare the photon MBRT (xMBRT), electron MBRT (eMBRT), and proton MBRT (pMBRT) approaches, we considered the treatment of a brain tumor located at a depth of 75 mm. Results Both mean energy deposition at micrometric scale and DNA damage in the “valley” cell nuclei were very low as compared with these parameters in the peak region at all depths for xMBRT and at depths of 0 to 30 mm and 0 to 50 mm for eMBRT and pMBRT, respectively. Only the charged minibeams were favorable for tumor control by producing similar effects in peak and valley cells after 70 mm. At the micrometer scale, the energy deposited per event pointed to a potential advantage of proton beams for tumor control, as more aggressive events could be expected at the end of their tracks. At the nanometer scale, all three MBRT modalities produced direct clustered DNA breaks, although the majority of damage (>93%) was composed of isolated single strand breaks. The pMBRT led to a significant increase in the proportion of clustered single strand breaks and double‐strand breaks at the end of its range as compared to the entrance (7% at 75 mm vs 3% at 10 mm) in contrast to eMBRT and xMBRT. In the latter cases, the proportions of complex breaks remained constant, irrespective of the depth and region (peak or valley). Conclusions Enhanced normal tissue sparing can be expected with these three MBRT techniques. Among the three modalities, pMBRT offers an additional gain for radioresistant tumors, as it resulted in a higher number of complex DNA damage clusters in the tumor region. These results can aid understanding of the biological mechanisms of MBRT.

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“…Recently, track-structure models for gold nanoparticles have also been developed and will be incorporated in the upcoming Geant4-DNA releases [83][84][85]. It also includes modelling of the chemical stage [86] and offers various representations of DNA target structures to be used in DNA damage studies [87][88][89]. Geant4-DNA can transport electrons (7.4 eV-1 MeV), protons (100 eV-100 MeV), alpha particles (1 keV-400 MeV), and ions (0.5 MeV/u-10 6 MeV/u).…”

Section: Particle Track Structure Codesmentioning

confidence: 99%

Ionizing Radiation and Complex DNA Damage: Quantifying the Radiobiological Damage Using Monte Carlo Simulations

Chatzipapas

Papadimitroulas²,

Emfietzoglou

et al. 2020

Cancers

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Ionizing radiation is a common tool in medical procedures. Monte Carlo (MC) techniques are widely used when dosimetry is the matter of investigation. The scientific community has invested, over the last 20 years, a lot of effort into improving the knowledge of radiation biology. The present article aims to summarize the understanding of the field of DNA damage response (DDR) to ionizing radiation by providing an overview on MC simulation studies that try to explain several aspects of radiation biology. The need for accurate techniques for the quantification of DNA damage is crucial, as it becomes a clinical need to evaluate the outcome of various applications including both low- and high-energy radiation medical procedures. Understanding DNA repair processes would improve radiation therapy procedures. Monte Carlo simulations are a promising tool in radiobiology studies, as there are clear prospects for more advanced tools that could be used in multidisciplinary studies, in the fields of physics, medicine, biology and chemistry. Still, lot of effort is needed to evolve MC simulation tools and apply them in multiscale studies starting from small DNA segments and reaching a population of cells.

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Influence of chromatin compaction on simulated early radiation‐induced DNA damage using Geant4‐DNA

Cited by 44 publications

References 39 publications

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

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

Minibeam radiation therapy: A micro‐ and nano‐dosimetry Monte Carlo study

Ionizing Radiation and Complex DNA Damage: Quantifying the Radiobiological Damage Using Monte Carlo Simulations

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