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Background and Aim: Cosmic rays have the potential to induce significant changes in atmospheric chemical reactions by generating ions, thereby influencing the atmosphere's chemical composition. The use of particle-molecule interaction models that account for the molecular structure of the atmospheric medium can advance our understanding on the role of ions, and enables a quantitative analysis of the impact of ion-molecule reactions on atmospheric modifications. This study marks the initial effort to expand the Geant-DNA toolkit for atmospheric applications., Methods: Building on our previous work, we extended the validation of new electron impact interaction models with the nitrogen and oxygen molecules up to 10 MeV. Additionally, we introduce electron cross sections for the carbon dioxide molecule, due to its crucial role as a major greenhouse gas. We present the implementation of the cross section models in Geant4-DNA, along with their validation through simulations of stopping power and range., Results: The differential cross sections have been verified against analytical calculations, demonstrating good agreement with existing literature data for all three molecules. The implementation has been validated through simulations of stopping power and range in N 2 , O 2 , CO 2 , and air. Results demonstrate agreement within 6% compared to reference data from the ESTAR database., Conclusions: The cross section models for the N 2 , O 2 , and CO 2 atmospheric molecules have been implemented in the Geant4-DNA toolkit. This evolution is crucial for studying ionic reactive chemical networks in a quantitative manner, assessing the impact of ionization on chemical reactions occurring in the atmosphere and their implications for climate., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Francesca Nicolanti reports was provided by University of Rome La Sapienza. Francesca Nicolanti reports a relationship with University of Rome La Sapienza that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Background: This study aimed to develop a novel human cell geometry for the Geant4-DNA simulation toolkit that explicitly incorporates all 23 chromosome pairs of the human cell. This approach contrasts with the existing, default human cell, geometrical model, which utilizes a continuous Hilbert curve., Methods: A Python-based tool named "complexDNA" was developed to facilitate the design of both simple and complex DNA geometries. This tool was employed to construct a human cell geometry with individual pairs of chromosomes. Subsequently, the performance of this chromosomal model was compared to the standard human cell model provided in the "molecularDNA" Geant4-DNA example., Results: Simulations using the new chromosomal model revealed minimal discrepancies in DNA damage yield and fragment size distribution compared to the default human cell model. Notably, the chromosomal model demonstrated significant computational efficiency, requiring approximately three times less simulation time to achieve equivalent results., Conclusions: This work highlights the importance of incorporating chromosomal structure into human cell models for radiation biology research. The "complexDNA" tool offers a valuable resource for creating intricate DNA structures for future studies. Further refinements, such as implementing smaller voxels for euchromatin regions, are proposed to enhance the model's accuracy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

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., (© 2024 American Association of Physicists in Medicine.)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Objective . The mechanisms of radiation-induced DNA damage can be understood via the fundamental acquisition of knowledge through a combination of experiments and modeling. Currently, most biological experiments are performed by irradiating an entire cell population, whereas modeling of radiation-induced effects is usually performed via Monte Carlo simulations with track structure codes coupled to realistic DNA geometries of a single-cell nucleus. However, the difference in scale between the two methods hinders a direct comparison because the dose distribution in the cell population is not necessarily uniform owing to the stochastic nature of the energy deposition. Thus, this study proposed the MINAS TIRITH tool to model the distribution of radiation-induced DNA damage in a cell population. Approach . The proposed method is based on precomputed databases of microdosimetric parameters and DNA damage distributions generated using the Geant4-DNA Monte Carlo Toolkit. First, a specific energyzwas assigned to each cell of an irradiated population for a particular absorbed doseDabs,following microdosimetric formalism. Then, each cell was assigned a realistic number of DNA damage events according to the specific energyz,respecting the stochastic character of its occurrence. Main results . This study validated the MINAS TIRITH tool by comparing its results with those obtained using the Geant4-DNA track structure code and a Geant4-DNA based simulation chain for DNA damage calculation. The different elements of comparison indicated consistency between MINAS TIRITH and the Monte Carlo simulation in case of the dose distribution in the population and the calculation of the amount of DNA damage. Significance . MINAS TIRITH is a new approach for the calculation of radiation-induced DNA damage at the cell population level that facilitates reasonable simulation times compared to those obtained with track structure codes. Moreover, this tool enables a more direct comparison between modeling and biological experimentation., (Creative Commons Attribution license.)

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.

Purpose: Simulation of indirect damage originating from the attack of free radical species produced by ionizing radiation on biological molecules based on the independent pair approximation is investigated in this work. In addition, a new approach, relying on the independent pair approximation that is at the origin of the independent reaction time (IRT) method, is proposed in the chemical stage of Geant4-DNA., Methods: This new approach has been designed to respect the current Geant4-DNA chemistry framework while proposing a variant IRT method. Based on the synchronous algorithm, this implementation allows us to access the information concerning the position of radicals and may make it more convenient for biological damage simulations. Estimates of the evolution of free species as well as biological hits in a segment of DNA chromatin fiber in Geant4-DNA were compared for the dynamic time step approach of the step-by-step (SBS) method, currently used in Geant4-DNA, and this newly implemented IRT., Results: Results show a gain in computation time of a factor of 30 for high LET particle tracks with a better than 10% agreement on the number of DNA hits between the value obtained with the IRT method as implemented in this work and the SBS method currently available in Geant4-DNA., Conclusion: Offering in Geant4-DNA more efficient methods for the chemical step based on the IRT method is a task in progress. For the calculation of biological damage, information on the position of chemical species is a crucial point. This can be achieved using the method presented in this paper., (© 2020 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

This study proposes an innovative approach to estimate relative biological effectiveness (RBE) of fast neutrons using the Geant4 toolkit. The Geant4-DNA version cannot track heavy ions below 0.5 MeV/nucleon. In order to explore the impact of this issue, secondary particles are simulated instead of the primary low-energy neutrons. The Evaluated Nuclear Data File library is used to determine the cross sections for the elastic and inelastic interactions of neutrons with water and to find the contribution of each secondary particle spectrum. Two strategies are investigated in order to find the best possible approach and results. The first one takes into account only light particles, protons produced from elastic scattering, and α particles from inelastic scattering. Geantino particles are shot instead of heavy ions; hence all heavy ions are considered in the simulations, though their physical effects on DNA not. The second strategy takes into account all the heavy and light ions, although heavy ions cannot be tracked down to very low energies (E<0.5 MeV/nucleon). Our model is based on the combination of an atomic resolution DNA geometrical model and a Monte Carlo simulation toolkit for tracking particles. The atomic coordinates of the DNA double helix are extracted from the Protein Data Bank. Since secondary particle spectra are used instead of simulating the interaction of neutrons explicitly, this method reduces the computation times dramatically. Double-strand break induction is used as the end point for the estimation of the RBE of fast neutrons. ^{60}Co γ rays are used as the reference radiation quality. Both strategies succeed in reproducing the behavior of the RBE&#95;{max} as a function of the incident neutron energy ranging from 0.1 to 14 MeV, including the position of its peak. A comparison of the behavior of the two strategies shows that for neutrons with energies less than 0.7 MeV, the effect of heavy ions would not be very significant, but above 0.7 MeV, heavy ions have an important role in neutron RBE.

Purpose: Track structure simulation codes can accurately reproduce the stochastic nature of particle-matter interactions in order to evaluate quantitatively radiation damage in biological cells such as DNA strand breaks and base damage. Such simulations handle large numbers of secondary charged particles and molecular species created in the irradiated medium. Every particle and molecular species are tracked step-by-step using a Monte Carlo method to calculate energy loss patterns and spatial distributions of molecular species inside a cell nucleus with high spatial accuracy. The Geant4-DNA extension of the Geant4 general-purpose Monte Carlo simulation toolkit allows for such track structure simulations and can be run on CPUs. However, long execution times have been observed for the simulation of DNA damage in cells. We present in this work an improvement of the computing performance of such simulations using ultraparallel processing on a graphical processing unit (GPU)., Methods: A new Monte Carlo simulator named MPEXS-DNA, allowing high computing performance by using a GPU, has been developed for track structure and radiolysis simulations at the subcellular scale. MPEXS-DNA physics and chemical processes are based on Geant4-DNA processes available in Geant4 version 10.02 p03. We have reimplemented the Geant4-DNA process codes of the physics stage (electromagnetic processes of charged particles) and the chemical stage (diffusion and chemical reactions for molecular species) for microdosimetry simulation by using the CUDA language. MPEXS-DNA can calculate a distribution of energy loss in the irradiated medium caused by charged particles and also simulate production, diffusion, and chemical interactions of molecular species from water radiolysis to quantitatively assess initial damage to DNA. The validation of MPEXS-DNA physics and chemical simulations was performed by comparing various types of distributions, namely the radial dose distributions for the physics stage, and the G-value profiles for each chemical product and their linear energy transfer dependency for the chemical stage, to existing experimental data and simulation results obtained by other simulation codes, including PARTRAC., Results: For physics validation, radial dose distributions calculated by MPEXS-DNA are consistent with experimental data and numerical simulations. For chemistry validation, MPEXS-DNA can also reproduce G-value profiles for each molecular species with the same tendency as existing experimental data. MPEXS-DNA also agrees with simulations by PARTRAC reasonably well. However, we have confirmed that there are slight discrepancies in G-value profiles calculated by MPEXS-DNA for molecular species such as H 2 and H 2 O 2 when compared to experimental data and PARTRAC simulations. The differences in G-value profiles between MPEXS-DNA and PARTRAC are caused by the different chemical reactions considered. MPEXS-DNA can drastically boost the computing performance of track structure and radiolysis simulations. By using NVIDIA's GPU devices adopting the Volta architecture, MPEXS-DNA has achieved speedup factors up to 2900 against Geant4-DNA simulations with a single CPU core., Conclusion: The MPEXS-DNA Monte Carlo simulation achieves similar accuracy to Monte Carlo simulations performed using other codes such as Geant4-DNA and PARTRAC, and its predictions are consistent with experimental data. Notably, MPEXS-DNA allows calculations that are, at maximum, 2900 times faster than conventional simulations using a CPU., (© 2018 The Authors Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

Purpose: Indirect biological damage due to reactive species produced in water radiolysis reactions is responsible for the majority of biological effect for low linear energy transfer (LET) radiation. Modeling water radiolysis and the subsequent interactions of reactive species, as well as track structures, is essential to model radiobiology on the microscale. Recently, chemistry models have been developed for Geant4-DNA to be used in combination with the comprehensive existing physics models. In the current work, the first detailed, independent, in silico validation of all species yields with published experimental observations and comparison with other radiobiological simulations is presented. Additionally, the effect of LET of protons and heavier ions on reactive species yield in the model was examined, as well as the completeness of the chemical reactions following the radiolysis within the time after physical interactions simulated in the model., Methods: Yields over time of reactive species were simulated for water radiolysis by incident electrons, protons, alpha particles, and ions with various LETs using Geant4 and RITRACKS simulation tools. Water dissociation and recombination was simulated using Geant4 to determine the completeness of chemical reactions at the end of the simulation. Yield validation was performed by comparing yields simulated using Geant4 with experimental observations and other simulations. Validation was performed for all species for low LET radiation and the solvated electron and hydroxyl radical for high LET ions., Results: It was found that the Geant4-DNA chemistry yields were generally in good agreement with experimental observations and other simulations. However, the Geant4-DNA yields for the hydroxyl radical and hydrogen peroxide at the end of the chemistry stage were found to be respectively considerably higher and lower than the experimentally observed yields. Increasing the LET of incident hadrons increased the yield of secondary species and decreased the yield of primary species. The effect of LET on the yield of the hydroxyl radical at 100 ns simulated with Geant4 was in good agreement with experimental measurements. Additionally, by the end of the simulation only 40% of dissociated water molecules had been recombined and the rate of recombination was slowing., Conclusions: The yields simulated using Geant4 are within reasonable agreement with experimental observations. Higher LET radiation corresponds with increased yields of secondary species and decreased yields of primary species. These trends combined with the LET having similar effects on the 100 ns hydroxyl radical yield for Geant4 and experimental measurements indicate that Geant4 accurately models the effect of LET on radiolysis yields. The limited recombination within the modeled chemistry stage and the slowing rate of recombination at the end of the stage indicate potential long-range indirect biological damage., (© 2018 American Association of Physicists in Medicine.)

The use of Monte Carlo (MC) simulations remains a powerful tool to study the biological effects induced by ionizing radiation on living beings. Several MC codes are commonly used in research fields such as nanodosimetry, radiotherapy, radiation protection, and space radiation. This work presents an enhancement of an existing model [1] for radiobiological purposes, to account for the indirect DNA damage induced by ionizing particles. The Geant4-DNA simulation toolkit was used to simulate the physical, pre-chemical, and chemical stages of early DNA damage induced by protons and α-particles. Liquid water was used as the medium for simulations. Two phase-space files were generated, one containing the energy deposition events and another with the position of chemical species produced by water radiolysis from 0.1 ps up to 1 ns. These files were used as input in the radiobiological code that contains the genetic material model with atomic resolution, consisting of several copies of 30 nm chromatin fibers. The B-DNA configuration was used. This work focused on the indirect damage produced by the hydroxyl radical (OH) attack on the sugar-phosphate group. The approach followed to account for the indirect DNA damage was the same as those used by other radiobiological codes [2,3]. The critical parameter considered here was the reaction radius, which was calculated from the Smoluchowski's diffusion equation. Single, double, and total strand break yields produced by direct, indirect, and mixed mechanisms are reported. The obtained results are consistent with experimental and calculation data sets published in the literature., (Copyright © 2018 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

In order to improve the understanding of the mechanisms involved in the generation of early DNA damage, a new calculation chain based on the Geant4-DNA toolkit was developed. This work presents for the first time the simulation of the physical, physicochemical and chemical stages of early radiation damage at the scale of an entire human genome (fibroblast, male) and using Geant4-DNA models. The DnaFabric software was extended to generate and export this nucleus model to a text file with a specific format that can be read by Geant4 user applications. This calculation chain was used to simulate the irradiation of the nucleus by primary protons of different energies (0,5; 0,7; 0,8; 1; 1,5; 2; 3; 4; 5; 10; 20 MeV) and the results, in terms of DNA double strand breaks, agree with experimental data found in the literature (pulsed field electrophoresis technique). These results show that the simulation is consistent and that its parameters are well balanced. Among the different parameters that can be adjusted, our results demonstrate that the criterion used to select direct strand break appears to have a very significant role on the final number of simulated double strand breaks.

A new alternative set of elastic and inelastic cross sections has been added to the very low energy extension of the Geant4 Monte Carlo simulation toolkit, Geant4-DNA, for the simulation of electron interactions in liquid water. These cross sections have been obtained from the CPA100 Monte Carlo track structure code, which has been a reference in the microdosimetry community for many years. They are compared to the default Geant4-DNA cross sections and show better agreement with published data. In order to verify the correct implementation of the CPA100 cross section models in Geant4-DNA, simulations of the number of interactions and ranges were performed using Geant4-DNA with this new set of models, and the results were compared with corresponding results from the original CPA100 code. Good agreement is observed between the implementations, with relative differences lower than 1% regardless of the incident electron energy. Useful quantities related to the deposited energy at the scale of the cell or the organ of interest for internal dosimetry, like dose point kernels, are also calculated using these new physics models. They are compared with results obtained using the well-known Penelope Monte Carlo code., (Copyright © 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Emerging radiotherapy treatments including targeted particle therapy, hadron therapy or radiosensitisation of cells by high-Z nanoparticles demand the theoretical determination of radiation track structure at the nanoscale. This is essential in order to evaluate radiation damage at the cellular and DNA level. Since 2007, Geant4 offers physics models to describe particle interactions in liquid water at the nanometre level through the Geant4-DNA Package. This package currently provides a complete set of models describing the event-by-event electromagnetic interactions of particles with liquid water, as well as developments for the modelling of water radiolysis. Since its release, Geant4-DNA has been adopted as an investigational tool in kV and MV external beam radiotherapy, hadron therapies using protons and heavy ions, targeted therapies and radiobiology studies. It has been benchmarked with respect to other track structure Monte Carlo codes and, where available, against reference experimental measurements. While Geant4-DNA physics models and radiolysis modelling functionalities have already been described in detail in the literature, this review paper summarises and discusses a selection of representative papers with the aim of providing an overview of a) geometrical descriptions of biological targets down to the DNA size, and b) the full spectrum of current micro- and nano-scale applications of Geant4-DNA., (Copyright © 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Understanding the fundamental mechanisms involved in the induction of biological damage by ionizing radiation remains a major challenge of today's radiobiology research. The Monte Carlo simulation of physical, physicochemical and chemical processes involved may provide a powerful tool for the simulation of early damage induction. The Geant4-DNA extension of the general purpose Monte Carlo Geant4 simulation toolkit aims to provide the scientific community with an open source access platform for the mechanistic simulation of such early damage. This paper presents the most recent review of the Geant4-DNA extension, as available to Geant4 users since June 2015 (release 10.2 Beta). In particular, the review includes the description of new physical models for the description of electron elastic and inelastic interactions in liquid water, as well as new examples dedicated to the simulation of physicochemical and chemical stages of water radiolysis. Several implementations of geometrical models of biological targets are presented as well, and the list of Geant4-DNA examples is described., (Copyright © 2015 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Protons are the dominant particles both in galactic cosmic rays and in solar particle events and, furthermore, proton irradiation becomes increasingly used in tumour treatment. It is believed that complex DNA damage is the determining factor for the consequent cellular response to radiation. DNA plasmid pBR322 was irradiated at U120-M cyclotron with 30 MeV protons and treated with two Escherichia coli base excision repair enzymes. The yields of SSBs and DSBs were analysed using agarose gel electrophoresis. DNA has been irradiated in the presence of hydroxyl radical scavenger (coumarin-3-carboxylic acid) in order to distinguish between direct and indirect damage of the biological target. Pure scavenger solution was used as a probe for measurement of induced OH· radical yields. Experimental OH· radical yield kinetics was compared with predictions computed by two theoretical models-RADAMOL and Geant4-DNA. Both approaches use Geant4-DNA for description of physical stages of radiation action, and then each of them applies a distinct model for description of the pre-chemical and chemical stage., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The purpose of this work is to evaluate the influence of the chromatin condensation on the number of direct double-strand break (DSB) damages induced by ions. Two geometries of chromosome territories containing either condensed or decondensed chromatin were implemented as biological targets in the Geant4 Monte Carlo simulation code and proton and alpha irradiation was simulated using the Geant4-DNA processes. A DBSCAN algorithm was used in order to detect energy deposition clusters that could give rise to single-strand breaks or DSBs on the DNA molecule. The results of this study show an increase in the number and complexity of DNA DSBs in condensed chromatin when compared with decondensed chromatin., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Purpose: Although DNA lesions are considered of prime importance for describing the post-irradiation cellular survival, they still remain rarely studied on both experimental and theoretical sides. Under these conditions, we here propose different theoretical models for predicting the single ionization and single capture total cross sections for DNA bases impacted by protons., Material and Methods: Three theoretical approaches are developed: a first classical one based on a classical trajectory Monte Carlo (CTMC) model and two quantum mechanical ones, namely, a Coulomb Born (CB1) and a continuum-distorted wave eikonal-initial-state (CDW-EIS) model., Results: Ionization and capture processes induced by protons on DNA bases (adenine, cytosine, thymine and guanine) are here studied in terms of total cross sections., Conclusions: A very good agreement is obtained between the different models at high enough impact velocities but discrepancies are observed between them at low impact energies (E(i) ≤ 100 keV). Furthermore, it is shown that the theoretical cross sections underestimate the rare existing experimental data in particular for adenine and thymine whereas a reasonable agreement is found for cytosine.

Purpose: With the advent of magnetic resonance imaging (MRI)-guided radiation therapy it is becoming increasingly important to consider the potential influence of a magnetic field on ionising radiation. This paper aims to study the effect of a magnetic field on the track structure of radiation to determine if the biological effectiveness may be altered., Methods: Using the Geant4-DNA (GEometry ANd Tracking 4) Monte Carlo simulation toolkit, nanodosimetric track structure parameters were calculated for electrons, protons and alpha particles moving in transverse magnetic fields up to 10 Tesla. Applying the model proposed by Garty et al., the track structure parameters were used to derive the probability of producing a double-strand break (DSB)., Results: For simulated primary particles of electrons (200 eV-10 keV), protons (300 keV-30 MeV) and alpha particles (1-9 MeV) the application of a magnetic field was shown to have no significant effect (within statistical uncertainty limits) on the parameters characterizing radiation track structure or the probability of producing a DSB., Conclusions: The null result found here implies that if the presence of a magnetic field were to induce a change in the biological effectiveness of radiation, the effect would likely not be due to a change in the track structure of the radiation.

Purpose: The invariance of the total direct strand break yield when DNA is irradiated by different types of particles and energies has been reported by previous works. This study is intended to explain the physical causes of this behavior., Methods: The GEANT4-DNA extension of the GEANT4 general purpose Monte Carlo simulation toolkit has been used to determine direct strand break yields induced by protons and alpha particles impacting on a B-DNA geometrical model, including five organization levels of the human genetic material. The linear energy transfer (LET) of such particles ranges from 4.8 keV/microm (10 MeV protons) to about 235 keV/microm (2 MeV alpha particles), at 5.225 pm depth (near the center of the region of interest). Direct total, single and double strand break probabilities have been determined in a liquid water homogeneous medium with a 1.06 g/cm3 density. The energetic spectra of single strand breaks (SSB), the number of energy deposition events, and the SSB/event ratio were determined., Results: The target-hit probability was found to be independent of both the type and the energy of the incident particle, even if this latter is a secondary electron. This probability is determined by the geometrical properties of the system. The total strand break yield and the number of energy deposition events required to reach a certain absorbed dose were found nearly independent of the type and energy of the incident ion (proton or alpha). In contrast, the double strand break (DSB) yield was found strongly dependent on the LET of the incident radiation., Conclusions: The SSB generation process is homogeneous and independent of the LET of the particles involved, at least within the proton and alpha particle energy range here studied. The target-hit probability is only determined by the ratio between the total volume occupied by targets and that of the ROI where the radiation deposits its energy. The maximum separation distance between two adjacent SSBs to produce a DSB is the parameter that breaks the homogeneity of the target-hit process, making the DSB production process strongly heterogeneous.

The ROSIRIS project aims to study the radiobiology of integrated systems for medical treatment optimisation using ionising radiations and evaluate the associated risk. In the framework of this project, one research focus is the interpretation of the initial radio-induced damage in DNA created by ionising radiation (and detected by γ-H2AX foci analysis) from the track structure of the incident particles. In order to calculate the track structure of ionising particles at a nanometric level, the Geant4 Monte Carlo toolkit was used. Geant4 (Object Oriented Programming Architecture in C++) offers a common platform, available free to all users and relatively easy to use. Nevertheless, the current low-energy threshold for electromagnetic processes in GEANT4 is set to 1 keV (250 eV using the Livermore processes), which is an unsuitable value for nanometric applications. To lower this energy threshold, the necessary interaction processes and models were identified, and the corresponding available cross sections collected from the literature. They are mostly based on the plane-wave Born approximation (first Born approximation, or FBA) for inelastic interactions and on semi-empirical models for energies where the FBA fails (at low energies). In this paper, the extensions that have been introduced into the 9.3 release of the Geant4 toolkit are described, the so-called Geant4-DNA extension, including a set of processes and models adapted in this study and permitting the simulation of electron (8 eV-1 MeV), proton (100 eV-100 MeV) and alpha particle (1 keV-10 MeV) interactions in liquid water.

The chemical stage of the Monte Carlo track-structure (MCTS) code Geant4-DNA was extended for its use in DNA strand break (SB) simulations and compared against published experimental data. Geant4-DNA simulations were performed using pUC19 plasmids (2686 base pairs) in a buffered solution of DMSO irradiated by60Co or137Csγ-rays. A comprehensive evaluation of SSB yields was performed considering DMSO, DNA concentration, dose and plasmid supercoiling. The latter was measured using the super helix density value used in a Brownian dynamics plasmid generation algorithm. The Geant4-DNA implementation of the independent reaction times method (IRT), developed to simulate the reaction kinetics of radiochemical species, allowed to score the fraction of supercoiled, relaxed and linearized plasmid fractions as a function of the absorbed dose. The percentage of the number of SB after •OH + DNA and H• + DNA reactions, referred as SSB efficiency, obtained using MCTS were 13.77% and 0.74% respectively. This is in reasonable agreement with published values of 12% and 0.8%. The SSB yields as a function of DMSO concentration, DNA concentration and super helix density recreated the expected published experimental behaviors within 5%, one standard deviation. The dose response of SSB and DSB yields agreed with published measurements within 5%, one standard deviation. We demonstrated that the developed extension of IRT in Geant4-DNA, facilitated the reproduction of experimental conditions. Furthermore, its calculations were strongly in agreement with experimental data. These two facts will facilitate the use of this extension in future radiobiological applications, aiding the study of DNA damage mechanisms with a high level of detail.

This Special Report presents a description of Geant4‐DNA user applications dedicated to the simulation of track structures (TS) in liquid water and associated physical quantities (e.g., range, stopping power, mean free path…). These example applications are included in the Geant4 Monte Carlo toolkit and are available in open access. Each application is described and comparisons to recent international recommendations are shown (e.g., ICRU, MIRD), when available. The influence of physics models available in Geant4‐DNA for the simulation of electron interactions in liquid water is discussed. Thanks to these applications, the authors show that the most recent sets of physics models available in Geant4‐DNA (the so‐called “option4” and “option 6” sets) enable more accurate simulation of stopping powers, dose point kernels, and W‐values in liquid water, than the default set of models (“option 2”) initially provided in Geant4‐DNA. They also serve as reference applications for Geant4‐DNA users interested in TS simulations. [ABSTRACT FROM AUTHOR]

Purpose: The GEANT4-DNA physics models are upgraded by a more accurate set of electron cross sections for ionization and excitation in liquid water. The impact of the new developments on lowenergy electron transport simulations by the GEANT4 Monte Carlo toolkit is examined for improving its performance in dosimetry applications at the subcellular and nanometer level. Methods: The authors provide an algorithm for an improved implementation of the Emfietzoglou model dielectric response function of liquid water used in the GEANT4-DNA existing model. The algorithm redistributes the imaginary part of the dielectric function to ensure a physically motivated behavior at the binding energies, while retaining all the advantages of the original formulation, e.g., the analytic properties and the fulfillment of the f -sum-rule. In addition, refinements in the exchange and perturbation corrections to the Born approximation used in the GEANT4-DNA existing model are also made. Results: The new ionization and excitation cross sections are significantly different from those of the GEANT4-DNA existing model. In particular, excitations are strongly enhanced relative to ionizations, resulting in higher W-values and less diffusive dose-point-kernels at sub-keV electron energies. Conclusions: An improved energy-loss model for the excitation and ionization of liquid water by low-energy electrons has been implemented in GEANT4-DNA. The suspiciously low W-values and the unphysical long tail in the dose-point-kernel have been corrected owing to a different partitioning of the dielectric function. [ABSTRACT FROM AUTHOR]

Abstract: This paper presents stopping power and ranges of electrons, protons, and alpha particles in liquid water, calculated using the latest Geant4-DNA processes implemented in the Geant4 Monte Carlo simulation toolkit. Inelastic cross sections are obtained using the first Born approximation and semi-empirical formulas like Rudd’s model for ionisation and the Miller and Green formula for excitation. Elastic collisions and vibrational excitations are considered for tracking electrons until complete thermalisation (0.025eV). A speed scaling procedure with an effective charge screening term was used to compute alpha particle and heavy ion cross sections. Geant4-DNA simulations were carried out using thin liquid water volumes to determine the linear energy loss (dE/dX), while larger volumes were used to obtain the particle range. While results converge for highly energetic particles, differences are observed for low energies when the applied theoretical models begin to diverge from each other. Results show a good agreement between the analytical calculations obtained from the models, the Geant4-DNA Monte Carlo simulation predictions and the data published in the ICRU reports. Geant4-DNA processes apply to the following energy ranges: 0.025eV–1MeV for electrons, 100eV–100MeV for protons and 1keV–400MeV for alpha particles in liquid water, however since experimental data for very low energies is scarce and very difficult to obtain these processes could not be thoroughly validated so they are recommended for energies above 1eV for electrons, 1keV for protons and 10keV for alpha particles. Relativistic, highly charged ions were implemented in our own “house” version of the code and will be available in future releases of Geant4. [Copyright &y& Elsevier]

Abstract: This paper presents a study of energy deposits induced by ionising particles in liquid water at the molecular scale. Particles track structures were generated using the Geant4-DNA processes of the Geant4 Monte-Carlo toolkit. These processes cover electrons (0.025eV–1MeV), protons (1keV–100MeV), hydrogen atoms (1keV–100MeV) and alpha particles (10keV–40MeV) including their different charge states. Electron ranges and lineal energies for protons were calculated in nanometric and micrometric volumes. [Copyright &y& Elsevier]