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Saga, Ryo*; Iwamori, Kenta*; Matsuya, Yusuke; Hosokawa, Yoichiro*
Computers in Biology and Medicine, 211, p.111743_1 - 111743_10, 2026/07
This study developed a biophysical model that integrates the characteristics of cancer stem cells (CSCs), including the side population (SP), and the oxygen enhancement effect (OER) to more accurately predict radiotherapy outcomes in prostate cancer. SP and main population (MP) cells were isolated from the DU145 prostate cancer cell line, and DNA double-strand breaks and survival were evaluated under both normoxic and hypoxic conditions (
0.1% O
). The obtained data were analyzed using the IMK model incorporating MP, SP, and oxygen concentration, and the predictions were compared with clinical tumor control probability (TCP) under various fractionation regimens (2, 3, and 7 Gy/Fx). As a result, the in vitro and clinical data were well reproduced by considering the MP/SP fraction, a population-independent OER, and the intratumoral hypoxic volume. Furthermore, the initial yield of DSBs was identified as a key determinant of radiosensitivity depending on cell characteristics and oxygen levels. The developed model is expected to contribute to the optimization of prostate cancer radiotherapy, including dose escalation to hypoxic tumor regions.
Kyriakou, I.*; Papadopoulos, A.*; Polopetrakis, I.*; Kotroumbelou, C.*; Plante, I.*; Matsuya, Yusuke; Kai, Takeshi; Qiu, R.*; Li, J.*; Kundr
t, P.*; et al.
Physics in Medicine & Biology, 71(8), p.085009_1 - 085009_25, 2026/04
Times Cited Count：0Several Monte Carlo Track-Structure (MCTS) codes for liquid water have been developed worldwide over the last 40 years; however, use the different interaction cross sections. This study evaluates the uncertainties of physical features (electronic stopping power, pathlength, dose-point-kernel, and microdosimetry) of low-energy electron transport in liquid water by using 6 types of MCTS codes. The intercomparison results reveal significant differences among MCTS codes at low energies, especially below ~100 eV, potentially compromising the accuracy of DNA damage simulations where such electrons play a key role. The present work highlights the need for further development of the physics models used in MCTS codes to reduce the uncertainties associated with low-energy electron transport calculations in liquid water.
:Ce using PHITS track-structure simulationsHirata, Yuho; Kai, Takeshi; Ogawa, Tatsuhiko; Matsuya, Yusuke; Sato, Tatsuhiko; Watanabe, Kenichi*; Kato, Takumi*; Kawaguchi, Noriaki*; Yanagida, Takayuki*
Radiation Measurements, 193, p.107651_1 - 107651_8, 2026/04
Times Cited Count：0 Percentile：0.00(Nuclear Science & Technology)CaF:Ce has a high potential to be used as a dosimeter due to its high optically stimulated luminescence (OSL) intensity. However, when phosphors such as CaF:Ce are irradiated with swift ions, the OSL intensity per dose decreases due to quenching effects. Traditionally, quenching effects in phosphors have been evaluated based on energy deposition density, using linear energy transfer (LET) as a metric. However, the relationship between quenching effects and LET varies with ion type, complicating unified evaluations. The track structure in PHITS can precisely simulate the radiation interactions. In this study, we simulated the detector response of CaF:Ce irradiated with swift-ions and compared these results with experimental data. The comparison suggests that the quantum yield of OSL is a critical parameter influencing the quenching effect in CaF:Ce. These findings are expected to contribute to the development of improved phosphor detectors.
value of hydrated electrons updated by a dynamic Monte Carlo simulationKai, Takeshi; Toigawa, Tomohiro; Matsuya, Yusuke*; Hirata, Yuho; Tsuchida, Hidetsugu*; Yokoya, Akinari*
RSC Advances (Internet), 16(15), p.13886 - 13895, 2026/03
Times Cited Count：0 Percentile：0.00(Chemistry, Multidisciplinary)Water is one of the most interesting subjects of research in life sciences and the power industry, yet the ratio of ionization to electron excitation in water radiolysis remains unclear. This ratio determines the yield of radiolytic chemical species, but currently, it is parameterized. We challenged this long-standing fundamental scientific problem using computer simulations and successfully evaluated the primary electron energy dependence of the initial yield of hydrated electrons without relying on conventional model parameters. Contrary to conventional concepts, this study revealed that defining cross sections for water ionization and electron excitation is unnecessary. Instead, the dynamic motion calculation of secondary electrons generated by water radiolysis determines the final ratio of ionization to excitation. Our novel analytical approach is expected to gradually recognized as a new method for analyzing general liquid radiolysis.
Fukunaga, Hisanori*; Seino, Ryosuke*; Matsuya, Yusuke; Takashima, Hiroyuki*; Ishikawa, Masayori*; Onodera, Yasuhito*; Shirato, Hiroki*; Miyata, Haruhiko*; Prise, K. M.*
Medcomm (Internet), 7(1), p.e70568_1 - e70568_11, 2026/01
The main purpose of reproductive toxicity testing is to evaluate whether the administration of xenobiotics, such as pharmaceuticals, food additives, and environmental chemicals, exerts adverse effects on reproductive function in living organisms. The outcomes can be applied as a scientific basis to evaluate potential risks to human reproductive health. In this study, we developed a novel luciferase reporter mouse model for assessing reproductive toxicity, enabling longitudinal and quantitative evaluations of male fertility through in vivo imaging of acrosin without the need for euthanasia. This approach promises to advance our understanding of the mechanisms underlying the onset and recovery of reproductive toxicity. Additionally, reducing the number of animals needed for evaluation aligns with the principle of Reduction, which is one of the core components of the 3Rs in animal studies.
Villagrasa, C.*; Baiocco, G.*; Chaoui, Z.-E.-A.*; Dingfelder, M.*; Incerti, S.*; Kundrt, P.*; Kyriakou, I.*; Matsuya, Yusuke; Kai, Takeshi; Parisi, A.*; et al.
PLOS ONE (Internet), 21(1), p.e0340500_1 - e0340500_22, 2026/01
Times Cited Count：3 Percentile：97.87(Multidisciplinary Sciences)Nanodosimetry, which is important for understanding the biological effects after ionizing radiation exposure, can be evaluated using Monte Carlo Track Structure (MCTS) codes that can reproduce atomic interactions at the molecular scale. Various MCTS codes, developed independently over decades, have used different physical models and cross section data sets for electron interactions in liquid water, that is the main component of biological tissues. In this study, we evaluated the uncertainties in nanodosimetric calculations due to the variation of interaction cross sections used in various MCTS codes. The calculation results of seven MCTS codes (i.e., Geant4-DNA, PARTRAC, PHITS, MCwater, and PTra) revealed that there were large differences in physical quantities at molecular scale, such as the average number of ionizations and the probability of two or more ionizations. The largest differences were observed for low-energy electrons, where the contribution of the interaction cross section was found to be the main cause of uncertainty. These results highlight that difference in the cross section have a non-negligible impact on biological effects, such as complex DNA damage induction.
CMatsuya, Yusuke; Yoshii, Yuji*; Kusumoto, Tamon*; Wang, Y.*; Ogawa, Tatsuhiko; Sato, Tatsuhiko; Kai, Takeshi
Scientific Reports (Internet), 24 Pages, 2026/00
Water radiolysis plays an important role in radiation effects on materials, such as DNA damage in the human body and corrosion processes in nuclear reactors. Conventional chemical simulation codes are generally limited to around room temperature, which differs significantly from the temperature conditions encountered in reactor environments. In this study, we developed a chemical simulation code (PHITS-Chem) based on the general-purpose Monte Carlo code, the Particle and Heavy Ion Transport code System (PHITS), applicable over a temperature range 0 to 350C. The code explicitly considers the temperature dependence of diffusion coefficients and reaction rate constants, and its performance was validated by comparing the calculated G-values with previously reported experimental and theoretical data for low-LET (0.2 keV/
m), medium-LET (11.9 keV/m), and high-LET (63.4 keV/m) radiation. The developed code enables high-precision evaluation of the reaction kinetics of radiolytic species over a wide temperature range and is expected to be useful for assessing in-core material degradation and for studies related to severe accident mitigation in nuclear reactors.
Ogawa, Tatsuhiko; Hirata, Yuho; Matsuya, Yusuke; Kai, Takeshi
Computer Physics Communications, 316, p.109758_1 - 109758_15, 2025/11
Times Cited Count：1 Percentile：51.60(Computer Science, Interdisciplinary Applications)A track structure simulation model, ITSART Ver.2, has been developed to simulate the transport of arbitrary ions in arbitrary materials, accounting for every atomic interaction on an event-by-event basis. Unlike conventional track structure models, which are typically designed for therapeutic particle beams or bio-molecular targets, ITSART Ver.2 uniquely enables track structure calculations for any ion-material combination across an energy range from 10 eV/n to 1 TeV/n. To validate the developed model, the energy-angular distributions of secondary electrons, ion stopping ranges, radial dose distributions, and microscopic dose distributions calculated by ITSART Ver.2 were benchmarked against literature data. The unique features of ITSART Ver.2, including kinetic modeling of secondary electrons above 1 keV, modeling of secondary electron angular distribution, consideration of momentum transfer to target atoms, and interface with an atomic de-excitation model, resulted in calculations that were consistent with the benchmarking data. Furthermore, this benchmarking calculation demonstrated that ITSART Ver.2 can reproduce target-specific quantities such as Auger electron production and penumbra radial dose, which cannot be simulated with conventional codes that approximate the target as water. The capability of ITSART Ver.2 to perform track structure calculations under unconventional conditions paves the way for simulating various irradiation eff ects, such as reactor material irradiation damage, semiconductor device degradation, and other complex interactions.
Matsuya, Yusuke; Saga, Ryo*; Wang, Y.*; Sato, Tatsuhiko
Medical Physics, 52(10), p.e70040_1 - e70040_14, 2025/09
Times Cited Count：0 Percentile：0.00(Radiology, Nuclear Medicine & Medical Imaging)Radiation-induced micronuclei (MN), which are chromosome fragments, are currently used as a quantitative indicator of the chromosomal aberrations detectable at a relatively early phase. The technique to assay the MN formation has been followed with increasing interest. However, the meaning of MN and the corresponding cellular responses remains uncertain. This study presents a biophysical model for estimating MN frequency by the extension of an integrated microdosimetric-kinetic (IMK) model that allows the prediction of cell survival after exposure, and theoretically explores the cellular responses associated with MN formation. By introducing a probability of MN formation from lethal lesions due to misrepair, our developed model enables the prediction of MN formation frequency depending on linear energy transfer and dose rate. Our model analyses confirmed that the relative biological effectiveness for cell survival and MN frequency are equivalent under the same irradiation conditions, indicating that MN is useful in both radiation therapy and radiation protection to quantitatively evaluate curative effects and histological damage at early stages after exposure.
Kai, Takeshi; Toigawa, Tomohiro; Matsuya, Yusuke*; Hirata, Yuho; Tsuchida, Hidetsugu*; Yokoya, Akinari*
Journal of Chemical Physics, 162(15), p.154102_1 - 154102_11, 2025/04
Times Cited Count：1 Percentile：41.78(Chemistry, Physical)Scientific knowledge of low-energy electrons resulting from water radiolysis is required to estimate radiation DNA damage. However, since the analysis of water radiolysis is very complex, this study focuses on the experimental values of low-energy electrons related to simple water photolysis and those generated by photoirradiation of electrodes in water. Both experimental analyses involve the presence or absence of a Coulomb field in the parent ion. In this study, we analyzed these experimental values using a calculation code that combines Monte Carlo and molecular dynamics methods. As a result, it was shown that the code reproduced the experimental values even under different experimental conditions, and the code was validated. The calculation code will be a powerful tool for analyzing the interaction between low-energy electrons and DNA, and is expected to be applied to elucidate the formation mechanism of radiation DNA damage.
Matsuya, Yusuke; Yoshii, Yuji*; Kusumoto, Tamon*; Ogawa, Tatsuhiko; Onishi, Seiki*; Hirata, Yuho; Sato, Tatsuhiko; Kai, Takeshi
Physical Chemistry Chemical Physics, 27(14), p.6887 - 6898, 2025/04
Times Cited Count：3 Percentile：79.67(Chemistry, Physical)Radicals by water radiolysis play an important role in evaluating radiation-induced biological effects, such as DNA damage induction, chromosomal aberrations, and carcinogenesis. In the Particle and Heavy Ion Transport code System (PHITS), a track-structure simulation mode enabling the estimation of each atomic interactions in water and a chemical simulation code (PHITS-Chem) dedicated to electron beams that can simulate radical dynamics have been developed in our previous study. Here, we developed the PHITS-Chem code applicable to any ion species, considering a space partitioning method to detect radical reactions more efficiently and the 4D visualization function. The updated PHITS-Chem code was verified by comparing the simulated G values of proton beams, 
particle beams, and carbon ion beams to the corresponding values in the literature. We succeeded in intuitively evaluating the diffusion dynamics of radicals using the PHITS 3D drawing software, PHIG-3D. The time to calculate the G values was reduced (e.g., about 28 times faster) while maintaining its calculation accuracy. The developed PHITS-Chem code is expected to contribute to precise and intuitive understanding of the biological effects induced by radicals in ion-beam radiotherapy.
Kai, Takeshi; Toigawa, Tomohiro; Matsuya, Yusuke*; Hirata, Yuho; Tsuchida, Hidetsugu*; Ito, Yuma*; Yokoya, Akinari*
Communications Chemistry (Internet), 8, p.60_1 - 60_9, 2025/03
Times Cited Count：4 Percentile：65.29(Chemistry, Multidisciplinary)Radiation DNA damage is formed from direct and indirect effects. The direct effect is the interaction between DNA and a radiation, while the indirect effect is the chemical reaction between DNA and radiolytic chemical species. We believed that when the direct effect is induced, multiple lesions are formed within 10 base pairs (about 3.4 nm) of DNA. The damage reduces repair efficiency and induces biological effects. In this study, DNA damage induced by only indirect effects was quantitatively evaluated. Our results indicated that the multiple damage is formed when only 10s of eV energy is deposited to water in the vicinity of DNA, although its formation probability is less than 1%. In other words, the possibility of late biological effects cannot be excluded simply by imparting energy to water in the extreme vicinity of DNA without direct interaction between radiation and DNA. Our results are one of the most important findings for understanding low-dose radiation risk.
Papadopoulos, A.*; Kyriakou, I.*; Matsuya, Yusuke; Cort
s-Giraldo, M. A.*; Galocha-Oliva, M.*; Plante, I.*; Steward, R. D.*; Tran, N. H.*; Li, W.*; Daglis, I. A.*; et al.
Radiation and Environmental Biophysics, 64(1), p.117 - 135, 2025/03
Times Cited Count：2 Percentile：71.89(Biology)Radiation quality for determining biological effects is commonly linked to the microdosimetric quantity, especially dose-mean lineal energy y
. Calculations of y can be performed by sophisticated Monte Carlo track structure (MCTS) codes. The y estimate depends on the type of the MCTS code and analysis model. This study focused on proton beams with 1 MeV-1 GeV, which are important in radiation protection, space applications, radiation therapy, etc., and compared the estimates of the y in liquid water by various MCTS codes (PHITS, RITRACK, and Geant4-DNA) and analysis models (refined Xapsos model). The comparison results showed that good agreement with the refined Xapsos model and various MCTS codes can be attained at less than 10-20% level, and Q values by the analytic model are also in better agreement with MCTS simulation data. These findings conclude that the refined analytic model might be used as an alternative to time- and CPU-intensive MCTS simulations and advance practical calculations of radiation qualities and risk assessment.
Hamada, Nobuyuki*; Matsuya, Yusuke; Zablotska, L. B.*; Little, M. P.*
Mutation Research; Reviews in Mutation Research, 795, p.108531_1 - 108531_38, 2025/01
Times Cited Count：6 Percentile：91.92(Biotechnology & Applied Microbiology)Biological effects of ionizing radiation vary not merely with total dose but also with temporal dose distribution. While sparing dose protraction effects where dose protraction reduces effects of radiation have widely been accepted and generally assumed in radiation protection, inverse dose protraction effects (IDPEs) where dose protraction enhances radiation effects have not been well recognized, nor comprehensively reviewed. Here, we review the current knowledge on IDPEs of low LET radiation. Since 1952, 136 biology, epidemiology or clinical papers have heretofore reported IDPEs following low-LET irradiation (i.e., photons, 
-rays, electrons, protons or helium ions) using cell-free macromolecules (DNA, proteins, or lipids), cultured mammalian cells, insects, animals, and human. In contrast to a growing body of phenomenological evidence for manifestations of IDPEs, there is limited knowledge on mechanistic underpinnings. This review will contribute to ongoing research into the mechanism and to the discussion of the implications of the scientific evidence for radiation protection.
Hamada, Nobuyuki*; Matsuya, Yusuke; Zablotska, L. B.*; Little, M. P.*
Mutation Research; Reviews in Mutation Research, 795, p.108530_1 - 108530_23, 2025/01
Times Cited Count：5 Percentile：91.92(Biotechnology & Applied Microbiology)Radiation-induced biological effects vary depending on the linear energy transfer (LET), which represents the quality of radiation. When exposed to high-LET radiation acutely, the biological effects are in general greater than those of low-LET radiation; however, the effects of dose protraction remain unclear. Here, we review the current knowledge on inverse dose protraction effects of high-LET radiations. To the best of our knowledge, we identified 79 biological or epidemiological papers published since 1967 on high-LET radiation, such as neutrons, deuterons, -particles, light ions, and heavy ions. These papers include biochemical changes in cell-free macromolecules, neoplastic transformation, cell death, DNA damage responses and gene expression changes in mammalian cell cultures of human or rodent origin, gene mutations, cytogenetic changes, cancer, non-cancer diseases (e.g., testicular effects, cataracts, cardiovascular diseases) and life shortening in non-human mammals, and induction of lung cancer and bone tumors in humans. Meanwhile, the number of the papers (i.e., 79 papers) is about half of that on low-LET radiation (i.e., 154 papers). Manifestations and mechanisms of IDPEs of high-LET radiation are far less understood than those of low-LET radiation, warranting further studies that will be pivotal to assess the implications for radiation protection.
Shiraishi, Yuta*; Matsuya, Yusuke; Fukunaga, Hisanori*
Physics in Medicine & Biology, 69(24), p.248002_1 - 248002_5, 2024/12
Times Cited Count：0 Percentile：0.00(Engineering, Biomedical)In 2024, we developed a mathematical model to predict the survival rate of living cells after ultra-high dose-rate irradiation (Shiraishi et al. 2024 Phys. Med. Biol. 69 015017). In 2024, Liew and Mairani commented on the need to consider oxygen concentration in the model and the issues to the data used for benchmark testing, and published a reply paper (Shiraishi et al. 2024, Phys. Med. Biol. 69, 108002). In response to this response, Liew and Mairani again suggested the need to consider oxygen concentration in the predictive model and potential problems with the data selection process used for benchmark testing. In this response, we further discuss the limitations of the current developed model and how to determine the model parameters needed for predicting cell survival (and the number of experimental data available for fitting). In conclusions, this paper additionally re-demonstrated that even when using only reliable DNA damage data after ultra-high dose-rate irradiation under normoxic conditions, the model could reproduce the measured survival data for various types of cell lines.
Ogawa, Tatsuhiko; Hirata, Yuho; Matsuya, Yusuke; Kai, Takeshi; Sato, Tatsuhiko; Iwamoto, Yosuke; Hashimoto, Shintaro; Furuta, Takuya; Abe, Shinichiro; Matsuda, Norihiro; et al.
EPJ Nuclear Sciences & Technologies (Internet), 10, p.13_1 - 13_8, 2024/11
The latest updates on PHITS, a versatile radiation transport code, focusing specifically on track-structure models are presented. Track structure calculations are methods used to simulate the movement of charged particles while explicitly considering each atomic reaction. Initially developed for radiation biology, these calculation methods aimed to analyze the radiation-induced damage to DNA and chromosomes. Several track-structure calculation models, including PHITS-ETS, PHITS-ETS for Si, PHITS-KURBUC, ETSART, and ITSART, have been developed and implemented to PHITS. These models allow users to study the behavior of various particles at the nano-scale across a wide range of materials. Furthermore, potential applications of track-structure calculations have also been proposed so far. This collection of track-structure calculation models, which encompasses diverse conditions, opens up new avenues for research in the field of radiation effects.
Matsuya, Yusuke; Kai, Takeshi; Sato, Tatsuhiko
Shototsu, 21(3), p.R008_1 - R008_8, 2024/11
Particle and Heavy Ion Transport code System PHITS is a Monte Carlo code that enables the simulation of the behavior of radiation using a computer. Since 2018, a track-structure mode has been developed that allows the simulation of each atomic interaction in liquid water, which is a main component of living organisms. This development has made it possible to perform high-spatial resolution radiation track-structure analysis on the DNA scale. Meanwhile, based on the spatial information of atomic interactions calculated in the track-structure mode, we have also succeeded in developing an analysis code that enables the estimate of the various types of DNA damage yields efficiently and with high accuracy. In this review, we introduce an overview of the track-structure mode and DNA damage estimation model implemented in the latest version of PHITS, and show examples of applications of PHITS in the field of life sciences.
Hirata, Yuho; Kai, Takeshi; Ogawa, Tatsuhiko; Matsuya, Yusuke; Sato, Tatsuhiko
Hoshasen Kagaku (Internet), (118), p.21 - 28, 2024/10
Accurate dose evaluation by radiation detectors is crucial for the safe use of radiation. However, with certain types of radiation, the output from detectors can be nonlinear relative to the dose, thereby hindering correct dose assessments. To address these issues, it is vital to theoretically analyze the mechanisms affecting detector outputs. The radiation transport code PHITS includes a track structure analysis mode that precisely tracks radiation behavior. This review paper introduces the newly developed Electron Trajectory Structure Analysis Mode for Arbitrary Materials (ETSART), which facilitates the tracking of electron beams in various detector materials. Additionally, we present an example of phosphor quenching under ion beam irradiation, as analyzed using the PHITS track structure mode.
Kai, Takeshi; Toigawa, Tomohiro; Matsuya, Yusuke*; Hirata, Yuho; Tezuka, Tomoya*; Tsuchida, Hidetsugu*; Yokoya, Akinari*
Scientific Reports (Internet), 14, p.24722_1 - 24722_15, 2024/10
Times Cited Count：5 Percentile：38.08(Multidisciplinary Sciences)Scientific insight of water radiolysis is essential to estimate the direct and indirect effects of radiation DNA damage. Secondary electrons produced by water radiolysis are responsible for both effects. Here, we use a first-principles code to calculate the femtosecond dynamics of secondary electrons produced as a result of 20-30 eV energy deposition to water and analyze the formation mechanism of radiolytic chemical species produced in a nano-size ultra-small space region. From the results, it was clarified that the chemical species produced by water radiolysis begin to densify in the ultra-small region of a few nanometers when the deposition energy exceeds 25 eV. Our results provide important scientific insights into the formation of clustered DNA damage, which is believed to cause biological effects such as cell death.
