Consideration of the dielectric response for radiation chemistry simulations.

The spur reaction, a spatially nonhomogeneous chemical reaction following ionization, is crucial in radiolysis or photolysis in liquids, but the spur expansion process has yet to be elucidated. One reason is the need to understand the role of the dielectric response of the solvating molecules surrounding the charged species generated by ionization. The dielectric response corresponds to the time evolution of the permittivity and might affect the chemical reaction-diffusion of the species in a spur expansion process. This study examined the competitive relationship between reaction-diffusion kinetics and the dielectric response by solving the Debye-Smoluchowski equation while considering the dielectric response. The Coulomb force between the charged species gradually decreases with the dielectric response. Our calculation results found a condition where fast recombination occurs before the dielectric response is complete. Although it has been reported that the primary G-values of free electrons depend on the static dielectric constant under low-linear-energy transfer radiation-induced ionization, we propose that considering the dielectric response can provide a deeper insight into fast recombination reactions under high-linear-energy transfer radiation- or photo-induced ionization. Our simulation method enables the understanding of fast radiation-induced phenomena in liquids.

A step-by-step simulation code for estimating yields of water radiolysis species based on electron track-structure mode in the PHITS code.

Objective. Time-dependent yields of chemical products resulting from water radiolysis play a great role in evaluating DNA damage response after exposure to ionizing radiation. Particle and Heavy Ion Transport code System (PHITS) is a general-purpose Monte Carlo simulation code for radiation transport, which simulates atomic interactions originating from discrete energy levels of ionizations and electronic excitations as well as molecular excitations as physical stages. However, no chemical code for simulating water radiolysis products exists in the PHITS package.Approach.Here, we developed a chemical simulation code dedicated to the PHITS code, hereafter calledPHITS-Chemcode, which enables the calculation of theGvalues of water radiolysis species (•OH, eaq-, H2, H2O2etc) by electron beams.Main results.The estimatedGvalues during 1 µs are in agreement with the experimental ones and other simulations. ThisPHITS-Chemcode also simulates the radiolysis in the presence of OH radical scavengers, such as tris(hydroxymethyl)aminomethane and dimethyl sulfoxide. Thank to this feature, the contributions of direct and indirect effects on DNA damage induction under various scavenging capacities can be analyzed.Significance.This chemical code coupled with PHITS could contribute to elucidating the mechanism of radiation effects by connecting physical, physicochemical, and chemical processes.

First-principles simulation of an ejected electron produced by monochromatic deposition energy to water at the femtosecond order.

This study uses a time-dependent first-principles simulation code to investigate the transient dynamics of an ejected electron produced in the monochromatic deposition energy from 11 to 19 eV in water. The energy deposition forms a three-body single spur comprising a hydroxyl radical (OH˙), hydronium ion (H3O+), and hydrated electron (eaq-). The earliest formation involves electron thermalization and delocalization dominated by the molecular excitation of water. Our simulation results show that the transient electron dynamics primarily depends on the amount of deposition energy to water; the thermalization time varies from 200 to 500 fs, and the delocalization varies from 3 to 10 nm in this energy range. These features are crucial for determining the earliest single-spur formation and facilitating a sequential simulation from an energy deposition to a chemical reaction in water photolysis or radiolysis. The spur radius obtained from the simulation correlates reasonably with the experimental-based estimations. Our results should provide universalistic insights for analysing ultrafast phenomena dominated by the molecular excitation of water in the femtosecond order.

Improvement of the hybrid approach between Monte Carlo simulation and analytical function for calculating microdosimetric probability densities in macroscopic matter.

Objective. Estimation of the probability density of the microdosimetric quantities in macroscopic matter is indispensable for applying the concept of microdosimetry to medical physics and radiological protection. The Particle and Heavy Ion Transport code System (PHITS) enables estimating the microdosimetric probability densities due to its unique hybrid modality between the Monte Carlo and analytical approaches called the microdosimetric function. It can convert the deposition energies calculated by the macroscopic Monte Carlo radiation transport simulation to microdosimetric probability densities in water using an analytical function based on the track-structure simulations.Approach. In this study, we improved this function using the latest track-structure simulation codes implemented in PHITS. The improved function is capable of calculating the probability densities of not only the conventional microdosimetric quantities such as lineal energy but also the number of ionization events occurring in a target site, the so-called ionization cluster size distribution, for arbitrary site diameters from 3 nm to 1µm.Main results. The accuracy of the improved function was well verified by comparing the microdosimetric probability densities measured by tissue-equivalent proportional counters with the corresponding data calculated in this study. Test calculations for clonogenic cell survival using the improved function coupled with the modified microdosimetric kinetic model suggested a slight increase of its relative biological effectiveness compared with our previous estimations. As a new application of the improved function, we calculated the relative biological effectiveness of the single-strand break and double-strand break yields for proton irradiations using the updated PHITS coupled with the simplified DNA damage estimation model, and confirmed its equivalence in accuracy and its superiority in computational time compared to our previously proposed method based on the track-structure simulation.Significance. From these features, we concluded that the improved function could expand the application fields of PHITS by bridging the gap between microdosimetry and macrodosimetry.

Nature of the physicochemical process in water photolysis uncovered by a computer simulation.

In this work, we investigate the physicochemical process of water photolysis to bridge physical and chemical processes by a newly developed first-principles calculation code. The deceleration, thermalization, delocalization, and initial hydration of the extremely low-energy electrons ejected by water photolysis are sequentially tracked in the condensed phase. We show herein the calculated results for these sequential phenomena during 300 fs. Our results indicate that the mechanisms heavily depend on the intermolecular vibration and rotation modes peculiar to water and the momentum transfer between the electrons and the water medium. We suggest that using our results for the delocalized electron distribution will reproduce successive chemical reactions measured by photolysis experiments using a chemical reaction code. We expect our approach to become a powerful technique for various scientific fields related to water photolysis and radiolysis.

Initial yield of hydrated electron production from water radiolysis based on first-principles calculation.

Many scientific insights into water radiolysis have been applied for developing life science, including radiation-induced phenomena, such as DNA damage and mutation induction or carcinogenesis. However, the generation mechanism of free radicals due to radiolysis remains to be fully understood. Consequently, we have encountered a crucial problem in that the initial yields connecting radiation physics to chemistry must be parameterized. We have been challenged in the development of a simulation tool that can unravel the initial free radical yields, from physical interaction by radiation. The presented code enables the first-principles calculation of low energy secondary electrons resulting from the ionization, in which the secondary electron dynamics are simulated while considering dominant collision and polarization effects in water. In this study, using this code, we predicted the yield ratio between ionization and electronic excitation from a delocalization distribution of secondary electrons. The simulation result presented a theoretical initial yield of hydrated electrons. In radiation physics, the initial yield predicted from parameter analysis of radiolysis experiments in radiation chemistry was successfully reproduced. Our simulation code helps realize a reasonable spatiotemporal connection from radiation physics to chemistry, which would contribute to providing new scientific insights for precise understanding of underlying mechanisms of DNA damage induction.

An Analytical Method for Quantifying the Yields of DNA Double-Strand Breaks Coupled with Strand Breaks by γ-H2AX Focus Formation Assay Based on Track-Structure Simulation.

Complex DNA double-strand break (DSB), which is defined as a DSB coupled with additional strand breaks within 10 bp in this study, induced after ionizing radiation or X-rays, is recognized as fatal damage which can induce cell death with a certain probability. In general, a DSB site inside the nucleus of live cells can be experimentally detected using the γ-H2AX focus formation assay. DSB complexity is believed to be detected by analyzing the focus size using such an assay. However, the relationship between focus size and DSB complexity remains uncertain. In this study, using Monte Carlo (MC) track-structure simulation codes, i.e., an in-house WLTrack code and a Particle and Heavy Ion Transport code System (PHITS), we developed an analytical method for qualifying the DSB complexity induced by photon irradiation from the microscopic image of γ-H2AX foci. First, assuming that events (i.e., ionization and excitation) potentially induce DNA strand breaks, we scored the number of events in a water cube (5.03 × 5.03 × 5.03 nm3) along electron tracks. Second, we obtained the relationship between the number of events and the foci size experimentally measured by the γ-H2AX focus formation assay. Third, using this relationship, we evaluated the degree of DSB complexity induced after photon irradiation for various X-ray spectra using the foci size, and the experimental DSB complexity was compared to the results estimated by the well-verified DNA damage estimation model in the PHITS code. The number of events in a water cube was found to be proportional to foci size, suggesting that the number of events intrinsically related to DSB complexity at the DNA scale. The developed method was applicable to focus data measured for various X-ray spectral situations (i.e., diagnostic kV X-rays and therapeutic MV X-rays). This method would contribute to a precise understanding of the early biological impacts of photon irradiation by means of the γ-H2AX focus formation assay.

Application of a simple DNA damage model developed for electrons to proton irradiation.

Proton beam therapy allows irradiating tumor volumes with reduced side effects on normal tissues with respect to conventional x-ray radiotherapy. Biological effects such as cell killing after proton beam irradiations depend on the proton kinetic energy, which is intrinsically related to early DNA damage induction. As such, DNA damage estimation based on Monte Carlo simulations is a research topic of worldwide interest. Such simulation is a mean of investigating the mechanisms of DNA strand break formations. However, past modellings considering chemical processes and DNA structures require long calculation times. Particle and heavy ion transport system (PHITS) is one of the general-purpose Monte Carlo codes that can simulate track structure of protons, meanwhile cannot handle radical dynamics simulation in liquid water. It also includes a simple model enabling the efficient estimation of DNA damage yields only from the spatial distribution of ionizations and excitations without DNA geometry, which was originally developed for electron track-structure simulations. In this study, we investigated the potential application of the model to protons without any modification. The yields of single-strand breaks, double-strand breaks (DSBs) and the complex DSBs were assessed as functions of the proton kinetic energy. The PHITS-based estimation showed that the DSB yields increased as the linear energy transfer (LET) increased, and reproduced the experimental and simulated yields of various DNA damage types induced by protons with LET up to about 30 keVµm-1. These results suggest that the current DNA damage model implemented in PHITS is sufficient for estimating DNA lesion yields induced after protons irradiation except at very low energies (below 1 MeV). This model contributes to evaluating early biological impacts in radiation therapy.

Impact of the Lorentz force on electron track structure and early DNA damage yields in magnetic resonance-guided radiotherapy.

Magnetic resonance-guided radiotherapy (MRgRT) has been developed and installed in recent decades for external radiotherapy in several clinical facilities. Lorentz forces modulate dose distribution by charged particles in MRgRT; however, the impact of Lorentz forces on low-energy electron track structure and early DNA damage induction remain unclear. In this study, we estimated features of electron track structure and biological effects in a static magnetic field (SMF) using a general-purpose Monte Carlo code, particle and heavy ion transport code system (PHITS) that enables us to simulate low-energy electrons down to 1 meV by track-structure mode. The macroscopic dose distributions by electrons above approximately 300 keV initial energy in liquid water are changed by both perpendicular and parallel SMFs against the incident direction, indicating that the Lorentz force plays an important role in calculating dose within tumours. Meanwhile, DNA damage estimation based on the spatial patterns of atomic interactions indicates that the initial yield of DNA double-strand breaks (DSBs) is independent of the SMF intensity. The DSB induction is predominantly attributed to the secondary electrons below a few tens of eV, of which energy deposition patterns are not considerably affected by the Lorentz force. Our simulation study suggests that treatment planning for MRgRT can be made with consideration of only changed dose distribution.

Track-structure modes in particle and heavy ion transport code system (PHITS): application to radiobiological research.

PURPOSE: In radiation physics, Monte Carlo radiation transport simulations are powerful tools to evaluate the cellular responses after irradiation. When investigating such radiation-induced biological effects, it is essential to perform track structure simulations by explicitly considering each atomic interaction in liquid water at the sub-cellular and DNA scales. The Particle and Heavy-Ion Transport code System (PHITS) is a Monte Carlo code which enables to calculate track structure at DNA scale by employing the track-structure modes for electrons, protons and carbon ions. In this paper, we review the recent development status and future prospects of the track-structure modes in the PHITS code. CONCLUSIONS: To date, the physical features of these modes have been verified using the available experimental data and Monte Carlo simulation results reported in literature. These track-structure modes can be used for calculating microdosimetric distributions to estimate cell survival and for estimating initial DNA damage yields. The use of PHITS track-structure mode is expected not only to clarify the underlying mechanisms of radiation effects but also to predict curative effects in radiation therapy. The results of PHITS simulations coupled with biophysical models will contribute to the radiobiological studies by precisely predicting radiation-induced biological effects based on the Monte Carlo approach.

Development and validation of proton track-structure model applicable to arbitrary materials.

A novel transport algorithm performing proton track-structure calculations in arbitrary materials was developed. Unlike conventional algorithms, which are based on the dielectric function of the target material, our algorithm uses a total stopping power formula and single-differential cross sections of secondary electron production. The former was used to simulate energy dissipation of incident protons and the latter was used to consider secondary electron production. In this algorithm, the incident proton was transmitted freely in matter until the proton produced a secondary electron. The corresponding ionising energy loss was calculated as the sum of the ionisation energy and the kinetic energy of the secondary electron whereas the non-ionising energy loss was obtained by subtracting the ionising energy loss from the total stopping power. The most remarkable attribute of this model is its applicability to arbitrary materials, i.e. the model utilises the total stopping power and the single-differential cross sections for secondary electron production rather than the material-specific dielectric functions. Benchmarking of the stopping range, radial dose distribution, secondary electron energy spectra in liquid water, and lineal energy in tissue-equivalent gas, against the experimental data taken from literature agreed well. This indicated the accuracy of the present model even for materials other than liquid water. Regarding microscopic energy deposition, this model will be a robust tool for analysing the irradiation effects of cells, semiconductors and detectors.

Verification of KURBUC-based ion track structure mode for proton and carbon ions in the PHITS code.

The particle and heavy ion transport code system (PHITS) is a general-purpose Monte Carlo radiation transport simulation code. It has the ability to handle diverse particle types over a wide range of energy. The latest PHITS development enables the generation of track structure for proton and carbon ions (1H+, 12C6+) based on the algorithms in the KURBUC code, which is considered as one of the most verified track-structure codes worldwide. This ion track-structure mode is referred to as the PHITS-KURBUC mode. In this study, the range, radial dose distributions, and microdosimetric distributions were calculated using the PHITS-KURBUC mode. Subsequently, they were compared with the corresponding data obtained from the original KURBUC and from other studies. These comparative studies confirm the successful inclusion of the KURBUC code in the PHITS code. As results of the synergistic effect between the macroscopic and microscopic radiation transport codes, this implementation enabled the detailed calculation of the microdosimetric and nanodosimetric quantities under complex radiation fields, such as proton beam therapy with the spread-out Bragg peak.

A Simplified Cluster Analysis of Electron Track Structure for Estimating Complex DNA Damage Yields.

Complex DNA damage, defined as at least two vicinal lesions within 10-20 base pairs (bp), induced after exposure to ionizing radiation, is recognized as fatal damage to human tissue. Due to the difficulty of directly measuring the aggregation of DNA damage at the nano-meter scale, many cluster analyses of inelastic interactions based on Monte Carlo simulation for radiation track structure in liquid water have been conducted to evaluate DNA damage. Meanwhile, the experimental technique to detect complex DNA damage has evolved in recent decades, so both approaches with simulation and experiment get used for investigating complex DNA damage. During this study, we propose a simplified cluster analysis of ionization and electronic excitation events within 10 bp based on track structure for estimating complex DNA damage yields for electron and X-ray irradiations. We then compare the computational results with the experimental complex DNA damage coupled with base damage (BD) measured by enzymatic cleavage and atomic force microscopy (AFM). The computational results agree well with experimental fractions of complex damage yields, i.e., single and double strand breaks (SSBs, DSBs) and complex BD, when the yield ratio of BD/SSB is assumed to be 1.3. Considering the comparison of complex DSB yields, i.e., DSB + BD and DSB + 2BD, between simulation and experimental data, we find that the aggregation degree of the events along electron tracks reflects the complexity of induced DNA damage, showing 43.5% of DSB induced after 70 kVp X-ray irradiation can be classified as a complex form coupled with BD. The present simulation enables us to quantify the type of complex damage which cannot be measured through in vitro experiments and helps us to interpret the experimental detection efficiency for complex BD measured by AFM. This simple model for estimating complex DNA damage yields contributes to the precise understanding of the DNA damage complexity induced after X-ray and electron irradiations.

A significant role of non-thermal equilibrated electrons in the formation of deleterious complex DNA damage.

Although most of the radiation damage to genomic DNA could be rendered harmless using repair enzymes in a living cell, a certain fraction of the damage is persistent resulting in serious genetic effects, such as mutation induction. In order to understand the mechanisms of the deleterious DNA damage formation in terms of its earliest physical stage at the radiation track end, dynamics of low energy electrons and their thermalization processes around DNA molecules were investigated using a dynamic Monte Carlo code. The primary incident (1 keV) electrons multiply collide within 1 nm (equivalent to three DNA-base-pairs, 3bp) and generate secondary electrons which show non-Gaussian and non-thermal equilibrium distributions within 300 fs. On the other hand, the secondary electrons are mainly distributed within approximately 10 nm from their parent cations although approximately 5% of the electrons are localized within 1 nm of the cations owing to the interaction of their Coulombic fields. The mean electron energy is 0.7 eV; however, more than 10% of the electrons fall into a much lower-energy region than 0.1 eV at 300 fs. These results indicate that pre-hydrated electrons are formed from the extremely decelerated electrons over a few nm from the cations. DNA damage sites comprising multiple nucleobase lesions or single strand breaks can therefore be formed by multiple collisions of these electrons within 3bp. This multiple damage site is hardly processed by base excision repair enzymes. However, pre-hydrated electrons can also be produced resulting in an additional base lesion (or a strand break) more than 3bp away from the multi-damage site. These damage sites may be finally converted into a double strand break (DSB) when base excision enzymes process the additional base lesions. This DSB includes another base lesion(s) at their termini, and may introduce miss-rejoining by DSB repair enzymes, and hence may result in biological effects such as mutation in surviving cells.

Dynamic Behavior of Secondary Electrons in Liquid Water at the Earliest Stage upon Irradiation: Implications for DNA Damage Localization Mechanism.

To clarify the formation of radiation damage in DNA, the dynamic behavior of low-energy secondary electrons produced by ionizing radiation in water was studied by using a dynamic Monte Carlo code that considers the Coulombic force between electrons and their parent cations. The calculated time evolution of the mean energy, total track length, and mean traveling distance of the electrons indicated that the prehydration of the electrons occurs competitively with thermalization on a time scale of hundreds of femtoseconds. The decelerating electrons are gradually attracted to their parent cations by Coulombic force within hundreds of femtoseconds, and finally about 12.6% electrons are distributed within 2 nm of the cations. The collision fraction for ionization and electronic excitation within 1 nm of the cation was estimated to be about 40%. If these electrons are decelerated in a living cell, they may cause highly localized lesions around a cation in a DNA molecule through additional dissociative electron transfer (DET) as well as ionization and electronic excitation (EXC), possibly resulting in cell death or mutation.

Deceleration processes of secondary electrons produced by a high-energy Auger electron in a biological context.

PURPOSE: To simulate the deceleration processes of secondary electrons produced by a high-energy Auger electron in water, and particularly to focus on the spatial and temporal distributions of the secondary electron and the collision events (e.g. ionization, electronic excitation, and dissociative electron attachment) that are involved in the multiplication of lesions at sites of DNA damage. MATERIALS AND METHODS: We developed a dynamic Monte Carlo code that considers the Coulombic force between an ejected electron and its parent cation produced by the Auger electron in water. Thus our code can simulate some return electrons to the parent cations. Using the code, we calculated to within the order of femtoseconds the temporal evolution of collision events, the mean energy, and the mean traveling distance (including its spatial probability distribution) of the electron at an ejected energy of 20 eV. RESULTS: Some of the decelerating electrons in water in the Coulombic field were attracted to the ionized atoms (cations) by the Coulombic force within hundreds of femtoseconds, although the force did not significantly enhance the number of ionization, electronic excitation, and dissociative electron attachment collision events leading to water radiolysis. CONCLUSIONS: The secondary electrons are decelerated in water by the Coulombic force and recombined to the ionized atoms (cations). Furthermore, the some return electrons might be prehydrated in water layer near the parent cation in DNA if the electrons might be emitted from the DNA. The prehydrated electron originated from the return electron might play a significant role in inducing DNA damage.

Evaluation of DNA damage induced by Auger electrons from 137Cs.

PURPOSE: To understand the biological effect of external and internal exposure from 137Cs, DNA damage spectrum induced by directly emitted electrons (γ-rays, internal conversion electrons, Auger electrons) from 137Cs was compared with that induced by 137Cs γ-rays. METHODS: Monte Carlo track simulation method was used to calculate the microscopic energy deposition pattern in liquid water. Simulation was performed for the two simple target systems in microscale. Radiation sources were placed inside for one system and outside for another system. To simulate the energy deposition by directly emitted electrons from 137Cs placed inside the system, the multiple ejections of electrons after internal conversion were considered. In the target systems, induction process of DNA damage was modeled and simulated for both direct energy deposition and the water radical reaction on the DNA. The yield and spatial distribution of simple and complex DNA damage including strand breaks and base lesions were calculated for irradiation by electrons and γ-rays from 137Cs. RESULTS: The simulation showed that the significant difference in DNA damage spectrum was not caused by directly ejected electrons and γ-rays from 137Cs. CONCLUSIONS: The result supports the existing perception that the biological effects by internal and external exposure by 137Cs are equivalent.

Development of a simulation method for dynamics of electrons ejected from DNA molecules irradiated with X-rays.

PURPOSE: To develop a method for simulating the dynamics of the photoelectrons and Auger electrons ejected from DNA molecules irradiated with pulsed monochromatic X-rays. MATERIALS AND METHODS: A 30-base-pair (bp) DNA molecule was used as the target model, and the X-rays were assumed to have a Gaussian-shaped time distribution. Photoionization and Auger decay were considered as the atomic processes. The atoms from which the photoelectrons or Auger electrons were emitted were specified in the DNA molecule (or DNA ion) using the Monte Carlo method, and the trajectory of each electron in the electric field formed around the positively charged DNA molecule was calculated with a Newtonian equation. The kinetics of the electrons produced by irradiation with X-rays at an intensity ranging from 1 × 10(12) to 1 × 10(16) photons/mm(2) and energies of 380 eV (below the carbon K-edge), 435 eV (above the nitrogen K-edge), and 560 eV (above the oxygen K-edge) were evaluated. RESULTS: It was found that at an X-ray intensity of 1 × 10(14) photons/mm(2) or less, all the produced electrons escaped from the target. However, above an X-ray intensity of 1 × 10(15) photons/mm(2) and an energy of 560 eV, some photoelectrons that were ejected from the oxygen atoms were trapped near the target DNA. CONCLUSIONS: A simulation method for studying the trajectories of electrons ejected from a 30-bp DNA molecule irradiated with pulsed monochromatic X-rays has been developed. The present results show that electron dynamics are strongly dependent on the charged density induced in DNA by pulsed X-ray irradiation.

Polarization of Healpha radiation due to anisotropy of fast-electron transport in ultraintense-laser-produced plasmas.

An atomic kinetics code is developed to gain insight into the generation of polarized Healpha by fast electron transport relevant to fast ignition. The calculation predicts a very small polarization in the dense region (>or=100 times the critical density) due to frequent elastic transitions between magnetic sublevels, while high polarization is observable in the low density region (