Most cited article - PubMed ID 26653251
Track structure modeling in liquid water: A review of the Geant4-DNA very low energy extension of the Geant4 Monte Carlo simulation toolkit
This roadmap reviews the new, highly interdisciplinary research field studying the behavior of condensed matter systems exposed to radiation. The Review highlights several recent advances in the field and provides a roadmap for the development of the field over the next decade. Condensed matter systems exposed to radiation can be inorganic, organic, or biological, finite or infinite, composed of different molecular species or materials, exist in different phases, and operate under different thermodynamic conditions. Many of the key phenomena related to the behavior of irradiated systems are very similar and can be understood based on the same fundamental theoretical principles and computational approaches. The multiscale nature of such phenomena requires the quantitative description of the radiation-induced effects occurring at different spatial and temporal scales, ranging from the atomic to the macroscopic, and the interlinks between such descriptions. The multiscale nature of the effects and the similarity of their manifestation in systems of different origins necessarily bring together different disciplines, such as physics, chemistry, biology, materials science, nanoscience, and biomedical research, demonstrating the numerous interlinks and commonalities between them. This research field is highly relevant to many novel and emerging technologies and medical applications.
- Publication type
- Journal Article MeSH
- Review MeSH
NASA has encouraged studies on 226Ra deposition in the human brain to investigate the effects of exposure to alpha particles with high linear energy transfer, which could mimic some of the exposure astronauts face during space travel. However, this approach was criticized, noting that radium is a bone-seeker and accumulates in the skull, which means that the radiation dose from alpha particles emitted by 226Ra would be heavily concentrated in areas close to cranial bones rather than uniformly distributed throughout the brain. In the high background radiation areas of Ramsar, Iran, extremely high levels of 226Ra in soil contribute to a large proportion of the inhabitants' radiation exposure. A prospective study on Ramsar residents with a calcium-rich diet was conducted to improve the dose uniformity due to 226Ra throughout the cerebral and cerebellar parenchyma. The study found that exposure of the human brain to alpha particles did not significantly affect working memory but was significantly associated with increased reaction times. This finding is crucial because astronauts on deep space missions may face similar cognitive impairments due to exposure to high charge and energy particles. The current study was aimed to evaluate the validity of the terrestrial model using the Geant4 Monte Carlo toolkit to simulate the interactions of alpha particles and representative cosmic ray particles, acknowledging that these radiation types are only a subset of the complete space radiation environment.
- Keywords
- Alpha particles, Monte Carlo simulation, Radiation, Radium, Space exploration,
- MeSH
- DNA MeSH
- Humans MeSH
- Linear Energy Transfer MeSH
- Monte Carlo Method MeSH
- Brain MeSH
- Prospective Studies MeSH
- Radium * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- DNA MeSH
- Radium * MeSH
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.
- Keywords
- DNA damage, geant4-DNA, plasmid, radiation chemistry, simulation, track-structure,
- MeSH
- Dimethyl Sulfoxide * MeSH
- DNA chemistry MeSH
- Nucleic Acid Conformation MeSH
- Monte Carlo Method MeSH
- Plasmids MeSH
- Computer Simulation MeSH
- DNA Damage * MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Dimethyl Sulfoxide * MeSH
- DNA MeSH
The chemical stage of the Monte Carlo track-structure simulation code Geant4-DNA has been revised and validated. The root-mean-square (RMS) empirical parameter that dictates the displacement of water molecules after an ionization and excitation event in Geant4-DNA has been shortened to better fit experimental data. The pre-defined dissociation channels and branching ratios were not modified, but the reaction rate coefficients for simulating the chemical stage of water radiolysis were updated. The evaluation of Geant4-DNA was accomplished with TOPAS-nBio. For that, we compared predicted time-dependentGvalues in pure liquid water for·OH, e-aq, and H2with published experimental data. For H2O2and H·, simulation of added scavengers at different concentrations resulted in better agreement with measurements. In addition, DNA geometry information was integrated with chemistry simulation in TOPAS-nBio to realize reactions between radiolytic chemical species and DNA. This was used in the estimation of the yield of single-strand breaks (SSB) induced by137Csγ-ray radiolysis of supercoiled pUC18 plasmids dissolved in aerated solutions containing DMSO. The efficiency of SSB induction by reaction between radiolytic species and DNA used in the simulation was chosen to provide the best agreement with published measurements. An RMS displacement of 1.24 nm provided agreement with measured data within experimental uncertainties for time-dependentGvalues and under the presence of scavengers. SSB efficiencies of 24% and 0.5% for·OH and H·, respectively, led to an overall agreement of TOPAS-nBio results within experimental uncertainties. The efficiencies obtained agreed with values obtained with published non-homogeneous kinetic model and step-by-step Monte Carlo simulations but disagreed by 12% with published direct measurements. Improvement of the spatial resolution of the DNA damage model might mitigate such disagreement. In conclusion, with these improvements, Geant4-DNA/TOPAS-nBio provides a fast, accurate, and user-friendly tool for simulating DNA damage under low linear energy transfer irradiation.
- Keywords
- DNA damage, Geant4-DNA, TOPAS-nBio, plasmid DNA, radiation chemistry, track structure, validation,
- MeSH
- Linear Energy Transfer MeSH
- Monte Carlo Method MeSH
- Computer Simulation MeSH
- DNA Damage * MeSH
- Water * MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Extramural MeSH
- Validation Study MeSH
- Names of Substances
- Water * MeSH
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.
- Keywords
- DNA damage, Geant4-DNA, IRT, diffusion-controlled reaction,
- MeSH
- Chromatin genetics MeSH
- DNA * genetics MeSH
- Monte Carlo Method MeSH
- DNA Damage * MeSH
- Reaction Time MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Chromatin MeSH
- DNA * MeSH
PURPOSE: The simulation of individual particle tracks and the chemical stage following water radiolysis in biological tissue is an effective means of improving our knowledge of the physico-chemical contribution to the biological effect of ionizing radiation. However, the step-by-step simulation of the reaction kinetics of radiolytic species is the most time-consuming task in Monte Carlo track-structure simulations, with long simulation times that are an impediment to research. In this work, we present the implementation of the independent reaction times (IRT) method in Geant4-DNA Monte Carlo toolkit to improve the computational efficiency of calculating G-values, defined as the number of chemical species created or lost per 100 eV of deposited energy. METHODS: The computational efficiency of IRT, as implemented, is compared to that from available Geant4-DNA step-by-step simulations for electrons, protons and alpha particles covering a wide range of linear energy transfer (LET). The accuracy of both methods is verified using published measured data from fast electron irradiations for • OH and e aq - for time-dependent G-values. For IRT, simulations in the presence of scavengers irradiated by cobalt-60 γ-ray and 2 MeV protons are compared with measured data for different scavenging capacities. In addition, a qualitative assessment comparing measured LET-dependent G-values with Geant4-DNA calculations in pure liquid water is presented. RESULTS: The IRT improved the computational efficiency by three orders of magnitude relative to the step-by-step method while differences in G-values by 3.9% at 1 μs were found. At 7 ps, • OH and e aq - yields calculated with IRT differed from recent published measured data by 5% ± 4% and 2% ± 4%, respectively. At 1 μs, differences were 9% ± 5% and 6% ± 7% for • OH and e aq - , respectively. Uncertainties are one standard deviation. Finally, G-values at different scavenging capacities and LET-dependent G-values reproduced the behavior of measurements for all radiation qualities. CONCLUSION: The comprehensive validation of the Geant4-DNA capabilities to accurately simulate the chemistry following water radiolysis is an ongoing work. The implementation presented in this work is a necessary step to facilitate performing such a task.
- Keywords
- Geant4-DNA, LET, Monte Carlo, independent reaction times, radiolysis, track-structure,
- MeSH
- Models, Chemical * MeSH
- DNA MeSH
- Linear Energy Transfer * MeSH
- Monte Carlo Method MeSH
- Computer Simulation MeSH
- Reaction Time MeSH
- Water MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- DNA MeSH
- Water MeSH
Track structure based simulations valuably complement experimental research on biological effects of ionizing radiation. They provide information at the highest level of detail on initial DNA damage induced by diverse types of radiation. Simulations with the biophysical Monte Carlo code PARTRAC have been used for testing working hypotheses on radiation action mechanisms, for benchmarking other damage codes and as input for modelling subsequent biological processes. To facilitate such applications and in particular to enable extending the simulations to mixed radiation field conditions, we present analytical formulas that capture PARTRAC simulation results on DNA single- and double-strand breaks and their clusters induced in cells irradiated by ions ranging from hydrogen to neon at energies from 0.5 GeV/u down to their stopping. These functions offer a means by which radiation transport codes at the macroscopic scale could easily be extended to predict biological effects, exploiting a large database of results from micro-/nanoscale simulations, without having to deal with the coupling of spatial scales and running full track-structure calculations.
- MeSH
- DNA Breaks, Double-Stranded radiation effects MeSH
- Humans MeSH
- Linear Energy Transfer MeSH
- Monte Carlo Method * MeSH
- DNA Damage * MeSH
- Protons * MeSH
- Radiotherapy * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Protons * MeSH
Our understanding of radiation-induced cellular damage has greatly improved over the past few decades. Despite this progress, there are still many obstacles to fully understand how radiation interacts with biologically relevant cellular components, such as DNA, to cause observable end points such as cell killing. Damage in DNA is identified as a major route of cell killing. One hurdle when modeling biological effects is the difficulty in directly comparing results generated by members of different research groups. Multiple Monte Carlo codes have been developed to simulate damage induction at the DNA scale, while at the same time various groups have developed models that describe DNA repair processes with varying levels of detail. These repair models are intrinsically linked to the damage model employed in their development, making it difficult to disentangle systematic effects in either part of the modeling chain. These modeling chains typically consist of track-structure Monte Carlo simulations of the physical interactions creating direct damages to DNA, followed by simulations of the production and initial reactions of chemical species causing so-called "indirect" damages. After the induction of DNA damage, DNA repair models combine the simulated damage patterns with biological models to determine the biological consequences of the damage. To date, the effect of the environment, such as molecular oxygen (normoxic vs. hypoxic), has been poorly considered. We propose a new standard DNA damage (SDD) data format to unify the interface between the simulation of damage induction in DNA and the biological modeling of DNA repair processes, and introduce the effect of the environment (molecular oxygen or other compounds) as a flexible parameter. Such a standard greatly facilitates inter-model comparisons, providing an ideal environment to tease out model assumptions and identify persistent, underlying mechanisms. Through inter-model comparisons, this unified standard has the potential to greatly advance our understanding of the underlying mechanisms of radiation-induced DNA damage and the resulting observable biological effects when radiation parameters and/or environmental conditions change.
