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Space radiation exposure from omnipresent Galactic Cosmic Rays (GCRs) in interplanetary space poses a serious carcinogenic risk to astronauts due to the-limited or absent-protective effect of the Earth's magnetosphere and, in particular, the terrestrial atmosphere. The radiation risk is directly influenced by the quality of the radiation, i.e., its pattern of energy deposition at the micron/DNA scale. For stochastic biological effects, radiation quality is described by the quality factor, [Formula: see text], which can be defined as a function of Linear Energy Transfer (LET) or the microdosimetric lineal energy ([Formula: see text]). In the present work, the average [Formula: see text] of GCR for different mission scenarios was calculated using a modified version of the microdosimetric Theory of Dual Radiation Action (TDRA). NASA's OLTARIS platform was utilized to generate the radiation environment behind different aluminum shielding (0-30 g/cm2) for a typical mission scenario in low-earth orbit (LEO) and in deep space. The microdosimetric lineal energy spectra of ions ([Formula: see text]) in 1 µm liquid water spheres were calculated by a generalized analytical model which considers energy-loss fluctuations and δ-ray transport inside the irradiated medium. The present TDRA-based [Formula: see text]-values for the LEO and deep space missions were found to differ by up to 10% and 14% from the corresponding ICRP-based [Formula: see text]-values and up to 3% and 6% from NASA's [Formula: see text]-model. In addition, they were found to be in good agreement with the [Formula: see text]-values measured in the International Space Station (ISS) and by the Mars Science Laboratory (MSL) Radiation Assessment Detector (RAD) which represent, respectively, a LEO and deep space orbit.
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Radiação Cósmica , Exposição à Radiação , Voo Espacial , Humanos , Astronautas , Eficiência Biológica Relativa , ÍonsRESUMO
Double-strand breaks (DSBs) in nuclear DNA represents radiation-induced damage that has been identified as particularly deleterious. Calculating this damage using Monte Carlo track structure modeling could be a suitable indicator to better assess and anticipate the side-effects of radiation therapy. However, as already demonstrated in previous work, the geometrical description of the nucleus and the DNA content used in the simulation significantly influence damage calculations. Therefore, in order to obtain accurate results, this geometry must be as realistic as possible. In this study, a new geometrical model of an endothelial cell nucleus and DNA distribution according to the isochore theory are presented and used in a Monte Carlo simulation chain based on the Geant4-DNA toolkit. In this theory, heterochromatin and euchromatin compaction are distributed along the genome according to five different families (L1, L2, H1, H2, and H3). Each of these families is associated with a different hetero/euchromatin rate related to its compaction level. In order to compare the results with those obtained using a previous nuclear geometry, simulations were performed for protons with linear energy transfers (LETs) of 4.29 keV/µm, 19.51 keV/µm, and 43.25 keV/µm. The organization of the chromatin fibers at different compaction levels linked to isochore families increased the DSB yield by 6-10%, and it allowed the most affected part of the genome to be identified. These new results indicate that the genome core is more radiosensitive than the genome desert, with a 3-8% increase in damage depending on the LET. This work highlights the importance of using realistic distributions of chromatin compaction levels to calculate radio-induced damage using Monte Carlo simulation methods.
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Eucromatina , Isocoros , Cromatina , DNA/química , Dano ao DNA , Eucromatina/genética , Humanos , Método de Monte CarloRESUMO
In this work, we use the next sub-volume method (NSM) to investigate the possibility of using the compartment-based ("on-lattice") model to simulate water radiolysis. We, first, start with a brief description of the reaction-diffusion master equation (RDME) in a spatially discretized simulation volume ("mesh"), which is divided into sub-volumes (or "voxels"). We then discuss the choice of voxel size and merging technique of a given mesh, along with the evolution of the system using the hierarchical algorithm for the RDME ("hRDME"). Since the compartment-based model cannot describe high concentration species of early radiation-induced spurs, we propose a combination of the particle-based step-by-step ("SBS") Brownian dynamics model and the compartment-based model ("SBS-RDME model") for the simulation. We, finally, use the particle-based SBS Brownian dynamics model of Geant4-DNA as a reference to test the model implementation through several benchmarks. We find that the compartment-based model can efficiently simulate the system with a large number of species and for longer timescales, beyond the microsecond, with a reasonable computing time. Our aim in developing this model is to study the production and evolution of reactive oxygen species generated under irradiation with different dose rate conditions, such as in FLASH and conventional radiotherapy.
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DNA/química , Transferência Linear de Energia , Modelos Moleculares , Água/química , Algoritmos , Simulação por Computador , Difusão , Modelos Químicos , Método de Monte Carlo , Radiólise de ImpulsoRESUMO
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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Dano ao DNA , Eucromatina/metabolismo , Heterocromatina/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Lesões Experimentais por Radiação/metabolismo , Animais , Relação Dose-Resposta à Radiação , Eucromatina/patologia , Heterocromatina/patologia , Células Endoteliais da Veia Umbilical Humana/patologia , Humanos , Método de Monte Carlo , Raios X/efeitos adversosRESUMO
In most patients with lung cancer radiation treatment is used either as single agent or in combination with radiosensitizing drugs. However, the mechanisms underlying combined therapy and its impact on different modes of cell death have not yet been fully elucidated. We aimed to examine effects of single and combined treatments with γ-rays and erlotinib on radioresistant CRL-5876 human lung adenocarcinoma cells with particular emphasis on cell death. CRL-5876 cells were treated with γ-rays and/or erlotinib and changes in cell cycle, DNA repair dynamics, ultrastructure, nuclear morphology and protein expression were monitored at different time points. To reveal the relationship between types of cell death that arise after these treatments, autophagy was blocked with chloroquine. We found that higher dose of γ-rays causes G2/M arrest while adding of erlotinib to this treatment decreases the number of cells in S phase. Impact of erlotinib on kinetics of disappearance of irradiation-induced DNA double strand breaks is reflected in the increase of residual γ-H2AX foci after 24 h. γ-rays provoke cytoprotective autophagy which precedes development of senescence. Erlotinib predominantly induces apoptosis and enlarges the number of apoptotic cells in the irradiated CRL-5876 cells. Chloroquine improved cytotoxicity induced by radiation and erlotinib, increased apoptosis and decreased senescence in the CRL-5876 cells. The results obtained on CRL-5876 cells indicate significant radiosensitizing effect of erlotinib and suggest that chloroquine in the combination with the above treatments may have an additional antitumor effect in lung adenocarcinoma.
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Adenocarcinoma/terapia , Cloridrato de Erlotinib/farmacologia , Raios gama/uso terapêutico , Neoplasias Pulmonares/terapia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Adenocarcinoma/radioterapia , Adenocarcinoma de Pulmão , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Autofagia/efeitos dos fármacos , Autofagia/efeitos da radiação , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/efeitos da radiação , Linhagem Celular Tumoral , Cloroquina/farmacologia , Quebras de DNA de Cadeia Dupla , Reparo do DNA , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/radioterapiaRESUMO
Clustered DNA damage induced by 10, 20 and 30 MeV protons in pBR322 plasmid DNA was investigated. Besides determination of strand breaks, additional lesions were detected using base excision repair enzymes. The plasmid was irradiated in dry form, where indirect radiation effects were almost fully suppressed, and in water solution containing only minimal residual radical scavenger. Simultaneous irradiation of the plasmid DNA in the dry form and in the solution demonstrated the contribution of the indirect effect as prevalent. The damage composition slightly differed when comparing the results for liquid and dry samples. The obtained data were also subjected to analysis concerning different methodological approaches, particularly the influence of irradiation geometry, models used for calculation of strand break yields and interpretation of the strand breaks detected with the enzymes. It was shown that these parameters strongly affect the results.
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Dano ao DNA , Plasmídeos/efeitos da radiação , Prótons/efeitos adversos , Quebras de DNA de Cadeia Dupla , Enzimas Reparadoras do DNA/metabolismo , Relação Dose-Resposta à Radiação , Eletroforese em Gel de Ágar , Raios gama/efeitos adversos , Transferência Linear de Energia , Modelos Biológicos , Plasmídeos/metabolismo , SoluçõesRESUMO
PURPOSE: Interdisciplinary scientific communities have shown large interest to achieve a mechanistic description of radiation-induced biological damage, aiming to predict biological results produced by different radiation quality exposures. Monte Carlo track-structure simulations are suitable and reliable for the study of early DNA damage induction used as input for assessing DNA damage. This study presents the most recent improvements of a Geant4-DNA simulation tool named "dsbandrepair". METHODS: "dsbandrepair" is a Monte Carlo simulation tool based on a previous code (FullSim) that estimates the induction of early DNA single-strand breaks (SSBs) and double-strand breaks (DSBs). It uses DNA geometries generated by the DNAFabric computational tool for simulating the induction of early single-strand breaks (SSBs) and double-strand breaks (DSBs). Moreover, the new tool includes some published radiobiological models for survival fraction and un-rejoined DSB. Its application for a human fibroblast cell and human umbilical vein endothelial cell containing both heterochromatin and euchromatin was conducted. In addition, this new version offers the possibility of using the new IRT-syn method for computing the chemical stage. RESULTS: The direct and indirect strand breaks, SSBs, DSBs, and damage complexity obtained in this work are equivalent to those obtained with the previously published simulation tool when using the same configuration in the physical and chemical stages. Simulation results on survival fraction and un-rejoined DSB are in reasonable agreement with experimental data. CONCLUSIONS: "dsbandrepair" is a tool for simulating DNA damage and repair, benchmarked against experimental data. It has been released as an advanced example in Geant4.11.2.
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Quebras de DNA de Cadeia Dupla , Reparo do DNA , Método de Monte Carlo , Humanos , Reparo do DNA/efeitos da radiação , Quebras de DNA de Cadeia Dupla/efeitos da radiação , Dano ao DNA , DNA/efeitos da radiação , Simulação por Computador , Células Endoteliais da Veia Umbilical Humana , Quebras de DNA de Cadeia Simples/efeitos da radiação , SoftwareRESUMO
Objective.To present a new set of lithium-ion cross-sections for (i) ionization and excitation processes down to 700 eV, and (ii) charge-exchange processes down to 1 keV u-1. To evaluate the impact of the use of these cross-sections on micro a nano dosimetric quantities in the context of boron neutron capture (BNC) applications/techniques.Approach.The Classical Trajectory Monte Carlo method was used to calculate Li ion charge-exchange cross sections in the energy range of 1 keV u-1to 10 MeV u-1. Partial Li ion charge states ionization and excitation cross-sections were calculated using a detailed charge screening factor. The cross-sections were implemented in Geant4-DNA v10.07 and simulations and verified using TOPAS-nBio by calculating stopping power and continuous slowing down approximation (CSDA) range against data from ICRU and SRIM. Further microdosimetric and nanodosimetric calculations were performed to quantify differences against other simulation approaches for low energy Li ions. These calculations were: lineal energy spectra (yf(y) andyd(y)), frequency mean lineal energyyF-, dose mean lineal energyyD-and ionization cluster size distribution analysis. Microdosimetric calculations were compared against a previous MC study that neglected charge-exchange and excitation processes. Nanodosimetric results were compared against pure ionization scaled cross-sections calculations.Main results.Calculated stopping power differences between ICRU and Geant4-DNA decreased from 33.78% to 6.9%. The CSDA range difference decreased from 621% to 34% when compared against SRIM calculations. Geant4-DNA/TOPAS calculated dose mean lineal energy differed by 128% from the previous Monte Carlo. Ionization cluster size frequency distributions for Li ions differed by 76%-344.11% for 21 keV and 2 MeV respectively. With a decrease in theN1within 9% at 10 keV and agreeing after the 100 keV. With the new set of cross-sections being able to better simulate low energy behaviors of Li ions.Significance.This work shows an increase in detail gained from the use of a more complete set of low energy cross-sections which include charge exchange processes. Significant differences to previous simulation results were found at the microdosimetric and nanodosimetric scales that suggest that Li ions cause less ionizations per path length traveled but with more energy deposits. Microdosimetry results suggest that the BNC's contribution to cellular death may be mainly due to alpha particle production when boron-based drugs are distributed in the cellular membrane and beyond and by Li when it is at the cell cytoplasm regions.
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Terapia por Captura de Nêutron de Boro , Lítio , Método de Monte Carlo , Radiometria , Lítio/química , Terapia por Captura de Nêutron de Boro/métodos , Nanotecnologia , ElasticidadeRESUMO
Exposure to ionizing radiation can induce genetic aberrations via unrepaired DNA strand breaks. To investigate quantitatively the dose-effect relationship at the molecular level, we irradiated dry pBR322 plasmid DNA with 3 MeV protons and assessed fragmentation yields at different radiation doses using long-read sequencing from Oxford Nanopore Technologies. This technology applied to a reference DNA model revealed dose-dependent fragmentation, as evidenced by read length distributions, showing no discernible radiation sensitivity in specific genetic sequences. In addition, we propose a method for directly measuring the single-strand break (SSB) yield. Furthermore, through a comparative study with a collection of previous works on dry DNA irradiation, we show that the irradiation protocol leads to biases in the definition of ionizing sources. We support this scenario by discussing the size distributions of nanopore sequencing reads in the light of Geant4 and Geant4-DNA simulation toolkit predictions. We show that integrating long-read sequencing technologies with advanced Monte Carlo simulations paves a promising path toward advancing our comprehension and prediction of radiation-induced DNA fragmentation.
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Fragmentação do DNA , Método de Monte Carlo , Plasmídeos , Plasmídeos/genética , Fragmentação do DNA/efeitos da radiação , Relação Dose-Resposta à Radiação , Análise de Sequência de DNA/métodos , Quebras de DNA de Cadeia Simples/efeitos da radiação , DNA/genéticaRESUMO
PURPOSE: Based on considerable interest to enlarge the experimental database of radioresistant cells after their irradiation with helium ions, HTB140, MCF-7 and HTB177 human malignant cells are exposed to helium ion beams having different linear energy transfer (LET). MATERIALS AND METHODS: The cells are irradiated along the widened 62 MeV/u helium ion Bragg peak, providing LET of 4.9, 9.8, 23.4 and 36.8 keV/µm. Numerical simulations with the Geant4 toolkit are used for the experimental design. Cell survival is evaluated and compared with reference γ-rays. DNA double strand breaks are assessed via γ-H2AX foci. RESULTS: With the increase of LET, surviving fractions at 2 Gy decrease, while RBE (2 Gy, γ) gradually increase. For HTB140 cells, above the dose of 4 Gy, a slight saturation of survival is observed while the increase of RBE (2 Gy, γ) remains unaffected. With the increase of LET the increase of γ-H2AX foci is revealed at 0.5 h after irradiation. There is no significant difference in the number of foci between the cell lines for the same LET. From 0.5 to 24 h, the number of foci drops reaching its residual level. For each time point, there are small differences in DNA DSB among the three cell lines. CONCLUSION: Analyses of data acquired for the three cell lines irradiated by helium ions, having different LET, reveal high elimination capacity and creation of a large number of DNA DSB with respect to γ-rays, and are between those reported for protons and carbon ions.
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BACKGROUND: Radiobiological effectiveness of radiation in cancer treatment can be studied at different scales (molecular till organ scale) and different time post irradiation. The production of free radicals and reactive oxygen species during water radiolysis is particularly relevant to understand the fundamental mechanisms playing a role in observed biological outcomes. The development and validation of Monte Carlo tools integrating the simulation of physical, physico-chemical and chemical stages after radiation is very important to maintain with experiments. PURPOSE: Therefore, in this study, we propose to validate a new Geant4-DNA chemistry module through the simulation of water radiolysis and Fricke dosimetry experiments on a proton preclinical beam line. MATERIAL AND METHODS: In this study, we used the GATE Monte Carlo simulation platform (version 9.3) to simulate a 67.5 MeV proton beam produced with the ARRONAX isochronous cyclotron (IBA Cyclone 70XP) at conventional dose rate (0.2 Gy/s) to simulate the irradiation of ultra-pure liquid water samples and Fricke dosimeter. We compared the depth dose profile with measurements performed with a plane parallel Advanced PTW 34045 Markus ionization chamber. Then, a new Geant4-DNA chemistry application proposed from Geant4 version 11.2 has been used to assess the evolution of HO ⢠${\mathrm{HO}}^ \bullet $ , e aq - ${\mathrm{e}}_{{\mathrm{aq}}}^ - $ , H 3 O + ${{\mathrm{H}}}_3{{\mathrm{O}}}^ + $ , H 2 O 2 ${{\mathrm{H}}}_2{{\mathrm{O}}}_2$ , H 2 ${{\mathrm{H}}}_2$ , HO 2 ⢠${\mathrm{HO}}_2^ \bullet $ , HO 2 - , O 2 ⢠- ${\mathrm{HO}}_2^ - ,{\mathrm{\ O}}_2^{ \bullet - }$ and HO - ${\mathrm{HO}}^ - $ reactive species along time until 1-h post-irradiation. In particular, the effect of oxygen and pH has been investigated through comparisons with experimental measurements of radiolytic yields for H 2 O 2 ${{\mathrm{H}}}_2{{\mathrm{O}}}_2$ and Fe3+. RESULTS: GATE simulations reproduced, within 4%, the depth dose profile in liquid water. With Geant4-DNA, we were able to reproduce experimental H 2 O 2 ${{\mathrm{H}}}_2{{\mathrm{O}}}_2$ radiolytic yields 1-h post-irradiation in aerated and deaerated conditions, showing the impact of small changes in oxygen concentrations on species evolution along time. For the Fricke dosimeter, simulated G(Fe3+) is 15.97 ± 0.2 molecules/100 eV which is 11% higher than the measured value (14.4 ± 04 molecules/100 eV). CONCLUSIONS: These results aim to be consolidated by new comparisons involving other radiolytic species, such as e aq - ${\mathrm{e}}_{{\mathrm{aq}}}^ - $ or , O 2 ⢠- $,{\mathrm{\ O}}_2^{ \bullet - }$ to further study the mechanisms underlying the FLASH effect observed at ultra-high dose rates (UHDR).
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A chemistry module has been implemented in Geant4-DNA since Geant4 version 10.1 to simulate the radiolysis of water after irradiation. It has been used in a number of applications, including the calculation of G-values and early DNA damage, allowing the comparison with experimental data. Since the first version, numerous modifications have been made to the module to improve the computational efficiency and extend the simulation to homogeneous kinetics in bulk solution. With these new developments, new applications have been proposed and released as Geant4 examples, showing how to use chemical processes and models. This work reviews the models implemented and application developments for modeling water radiolysis in Geant4-DNA as reported in the ESA BioRad III Project.
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INTRODUCTION: The electron ionization cross section of water is one of the most important input in Monte Carlo studies of cellular radiobiological effects. Analytical cross section models of the binary-encounter type have the potential of reducing simulation time and facilitate application to a variety of biological materials (other than water). The Binary-Encounter-Bethe (BEB) and Binary-Encounter-Dipole (BED) models of NIST are perhaps the most popular of such models giving reliable results for atoms and molecules in the gas-phase over a wide energy range. However, the use of such models to sub-keV electron energies in liquid water raises concerns due to the neglect of condensed phase effects that leads to a significant overestimation when compared to medium-specific dielectric models. PURPOSE: To modify the BEB and BED models towards better agreement with the recommended low-energy dielectric model of Geant4-DNA (Option 4). To implement the new modifications to the existing BEB model of the Option 6 physics constructor of Geant4-DNA and re-evaluate fundamental transport quantities for sub-keV electrons. METHODS: In analogy to a Yukawa potential a simple, yet physically-motivated, modification of the Burgess correction term is proposed to account for the reduction of the Coulomb interaction due to the polarizability of the target. The magnitude of the correction is guided by the dielectric-based ionization cross section implemented in Option 4. RESULTS: Differential, total and stopping ionization cross sections for low-energy electrons in liquid water are presented. When combined with the Vriens correction (which is not included in Option 6), the proposed modification to the BEB and BED models brings the ionization and stopping cross sections in much better agreement against those used in the Option 4 dielectric model of Geant4-DNA, with up to 30% and 10% deviation, respectively. Implementation of the new correction to the Option 6 constructor of Geant4-DNA and re-evaluation of fundamental transport quantities, such as electron penetration ranges and dose-point-kernels, reduced the discrepancies from Option 4 at sub-keV energies from 20 to 100% (or more) to well below 10% in most cases. CONCLUSIONS: A simple modification to the BEB and BED analytic models was found to improve their performance for sub-keV electrons in liquid water medium. Implementation of the new modification to the Option 6 constructor of Geant4-DNA significantly improved the agreement with the recommended low-energy Option 4 constructor for a variety of fundamental quantities related to electron transport.
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FLASH radiotherapy is a promising approach to cancer treatment that offers several advantages over conventional radiotherapy. With this novel technique, high doses of radiation are delivered in a short period of time, inducing the so-called FLASH effect - a phenomenon characterized by healthy tissue sparing without alteration of tumor control. The mechanisms behind the FLASH effect remain unknown. One way to approach this problem is to gain insight into the initial parameters that can distinguish FLASH from conventional irradiation by simulating particle transport in aqueous media using the general-purpose Geant4 Monte Carlo toolkit and its Geant4-DNA extension. This review article discusses the current status of Geant4 and Geant4-DNA simulations to investigate mechanisms underlying the FLASH effect, as well as the challenges faced in this research field. One of the primary challenges is to accurately simulate the experimental irradiation parameters. Another challenge is the temporal extension of the simulations. This review also focuses on two hypotheses to explain the FLASH effect - namely the oxygen depletion hypothesis and the inter-track interactions hypothesis - and discusses how the Geant4 toolkit can be used to investigate them. The aim of this review is to provide an overview of Geant4 and Geant4-DNA simulations for FLASH radiotherapy and to highlight the challenges that need to be overcome in order to better study the FLASH effect.
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DNA , Método de Monte CarloRESUMO
PURPOSE: This paper presents the capabilities of the Geant4-DNA Monte Carlo toolkit to simulate water radiolysis with scavengers using the step-by-step (SBS) or the independent reaction times (IRT) methods. It features two examples of application areas: (1) computing the escape yield of H2O2 following a 60Co γ-irradiation and (2) computing the oxygen depletion in water irradiated with 1 MeV electrons. METHODS: To ease the implementation of the chemical stage in Geant4-DNA, we developed a user interface that helps define the chemical reactions and set the concentration of scavengers. The first application area example required two computational steps to perform water radiolysis using NO2- and NO3- as scavengers and a 60Co irradiation. The oxygen depletion computation technique for the second application area example consisted of simulating track segments of 1 MeV electrons and determining the radio-induced loss and gain of oxygen molecules. RESULTS: The production of H2O2 under variable scavenging levels is consistent with the literature; the mean relative difference between the SBS and IRT methods is 7.2 % ± 0.5 %. For the oxygen depletion 1 µs post-irradiation, the mean relative difference between both methods is equal to 9.8 % ± 0.3 %. The results in the microsecond scale depend on the initial partial pressure of oxygen in water. In addition, the computed oxygen depletions agree well with the literature. CONCLUSIONS: The Geant4-DNA toolkit makes it possible to simulate water radiolysis in the presence of scavengers. This feature offers perspectives in radiobiology, with the possibility of simulating cell-relevant scavenging mechanisms.
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Peróxido de Hidrogênio , Água , Água/química , Radiobiologia/métodos , DNA/química , Método de Monte Carlo , Simulação por ComputadorRESUMO
Diffusing alpha-emitters radiation Therapy (DaRT) is an interstitial brachytherapy technique using 224Ra seeds. For accurate treatment planning a good understanding of the early DNA damage due to α-particles is required. Geant4-DNA was used to calculate the initial DNA damage and radiobiological effectiveness due to α-particles with linear energy transfer (LET) values in the range 57.5-225.9 keV/µm from the 224Ra decay chain. The impact of DNA base pair density on DNA damage has been modelled, as this parameter varies between human cell lines. Results show that the quantity and complexity of DNA damage changes with LET as expected. Indirect damage, due to water radical reactions with the DNA, decreases and becomes less significant at higher LET values as shown in previous studies. As expected, the yield of complex double strand breaks (DSBs), which are harder for a cell to repair, increases approximately linearly with LET. The level of complexity of DSBs and radiobiological effectiveness have been found to increase with LET as expected. The quantity of DNA damage has been shown to increase for increased DNA density in the expected base pair density range of human cells. The change in damage yield as a function of base pair density is largest for higher LET α-particles, an increase of over 50% for individual strand breaks between 62.7 and 127.4 keV/µm. This change in yield shows that the DNA base pair density is an important parameter for modelling DNA damage particularly at higher LET where the DNA damage is greatest and most complex.
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Braquiterapia , Humanos , Método de Monte Carlo , Dano ao DNA , Partículas alfa/uso terapêutico , DNARESUMO
PURPOSE: This study aimed to develop a computational environment for the accurate simulation of human cancer cell irradiation using Geant4-DNA. New cell geometrical models were developed and irradiated by alpha particle beams to induce DNA damage. The proposed approach may help further investigation of the benefits of external alpha irradiation therapy. METHODS: The Geant4-DNA Monte Carlo (MC) toolkit allows the simulation of cancer cell geometries that can be combined with accurate modelling of physical, physicochemical and chemical stages of liquid water irradiation, including radiolytic processes. Geant4-DNA is used to calculate direct and non-direct DNA damage yields, such as single and double strand breaks, produced by the deposition of energy or by the interaction of DNA with free radicals. RESULTS: In this study, the "molecularDNA" example application of Geant4-DNA was used to quantify early DNA damage in human cancer cells upon irradiation with alpha particle beams, as a function of linear energy transfer (LET). The MC simulation results are compared to experimental data, as well as previously published simulation data. The simulation results agree well with the experimental data on DSB yields in the lower LET range, while the experimental data on DSB yields are lower than the results obtained with the "molecularDNA" example in the higher LET range. CONCLUSION: This study explored and demonstrated the possibilities of the Geant4-DNA toolkit together with the "molecularDNA" example to simulate the helium beam irradiation of cancer cell lines, to quantify the early DNA damage, or even the following DNA damage response.
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Hélio , Neoplasias , Humanos , Simulação por Computador , Transferência Linear de Energia , DNA , Método de Monte Carlo , Dano ao DNA , Neoplasias/radioterapiaRESUMO
PURPOSE: Track structure Monte Carlo (MC) codes have achieved successful outcomes in the quantitative investigation of radiation-induced initial DNA damage. The aim of the present study is to extend a Geant4-DNA radiobiological application by incorporating a feature allowing for the prediction of DNA rejoining kinetics and corresponding cell surviving fraction along time after irradiation, for a Chinese hamster V79 cell line, which is one of the most popular and widely investigated cell lines in radiobiology. METHODS: We implemented the Two-Lesion Kinetics (TLK) model, originally proposed by Stewart, which allows for simulations to calculate residual DNA damage and surviving fraction along time via the number of initial DNA damage and its complexity as inputs. RESULTS: By optimizing the model parameters of the TLK model in accordance to the experimental data on V79, we were able to predict both DNA rejoining kinetics at low linear energy transfers (LET) and cell surviving fraction. CONCLUSION: This is the first study to demonstrate the implementation of both the cell surviving fraction and the DNA rejoining kinetics with the estimated initial DNA damage, in a realistic cell geometrical model simulated by full track structure MC simulations at DNA level and for various LET. These simulation and model make the link between mechanistic physical/chemical damage processes and these two specific biological endpoints.
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Dano ao DNA , Prótons , Cricetinae , Animais , Sobrevivência Celular , Cinética , DNA/química , Método de Monte CarloRESUMO
PURPOSE: We explored different technologies to minimize simulation time of the Monte-Carlo method for track generation following the Geant4-DNA processes for electrons in water. METHODS: A GPU software tool is developed for electron track simulations. A similar CPU version is also developed using the same collision models. CPU simulations were carried out on a single user desktop computer and on the computing grid France Grilles using 10 and 100 computing nodes. Computing time results for CPU, GPU, and grid simulations are compared with those using Geant4-DNA processes. RESULTS: The CPU simulations better performs when the number of electrons is less than 104 with 100 eV initial energy, this number decreases as the energy increases. The GPU simulations gives better results when the number of electrons is more than 104 with initial energy of 100 eV, this number decreases to 103 for electrons with 10KeV and increases back with higher energy. The use of the grid introduces an additional queuing time which slows down the overall simulation performance. Thus, the Grid gives better performance when the number of electrons is over 105 with initial energy of 10KeV, and this number decreases as the energy increases. CONCLUSIONS: The CPU is best suited for small numbers of primary incident electrons. The GPU is best suited when the number of primary incident particles occupies sufficient resources on GPU card in order to get an important computing power. The grid is best suited for simulations with high number of primary incident electrons with high initial energy.
Assuntos
Elétrons , Água , França , DNARESUMO
To facilitate the use of Geant4-DNA for radiation transport simulations in micro- and nanodosimeters, which are physically operated with tissue-equivalent gases such as nitrogen (and propane), this work aims to extend the cross section data available in Geant4-DNA to include those of nitrogen for electron energies ranging from 1 MeV down to the ionisation threshold. To achieve this, interaction cross section data for nitrogen that have been used with the in-house PTB PTra track structure code have been implemented in the current state-of-the-art Geant4-DNA simulation toolkit. An intercomparison has been performed between the two codes to validate this implementation. To quantify the agreement between the cross section models for nitrogen adopted in PTra and those implemented in Geant4-DNA, the simulation results of both codes were analysed using three physical parameters describing the ionisation cluster size distribution (ICSD): mean ionisation cluster size, variance of the cluster size and the probability to obtain a single ionisation within the target. Statistical analysis of the results indicates that the interaction cross section models for nitrogen used in PTra (elastic scattering, impact ionisations and electronic excitations) have been successfully implemented in Geant4-DNA. In addition, simulated ICSDs were compared to those measured with the Jet Counter nanodosimeter for energies between 100 and 2000 eV. For greater energies, the ICRP data for LET and particle range were used as a reference. The modified Geant4-DNA code and data successfully passed all these benchmarks fulfilling the requirement for their public release in the next version of the Geant4 toolkit.