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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：0Radiation 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.
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：2 Percentile：97.30(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：2 Percentile：97.30(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.
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, 19 Pages, 2025/00
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.
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.
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：0 Percentile：0.00(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.
Tsuchida, Hidetsugu*; Tezuka, Tomoya*; Kai, Takeshi; Matsuya, Yusuke*; Majima, Takuya*; Saito, Manabu*
Journal of Chemical Physics, 161(10), p.104503_1 - 104503_8, 2024/09
Times Cited Count：0 Percentile：0.00(Chemistry, Physical)Although fast ion beams can damage DNA by chemical products such as secondary electrons produced by their interaction with water in living cells, the process of formation of these chemical products in the Bragg peak region used in particle therapy is not fully understood. To investigate this process, we performed experiments to evaluate the yields of radiolytic products produced when a liquid water jet in vacuum is irradiated with a MeV-energy carbon beam. In addition, ionization processes in water due to incident ions and secondary electrons were simulated using a radiation transport Monte Carlo code. The results indicated that the primary source of ionization in water is secondary electrons. Finally, we show that these elementary processes contribute to the development of radiation biophysics and biochemistry to study the formation mechanism of DNA damage.
and 
study of biological effects on cancer cells in the presence of metallic materials during radiotherapyNagano, Takuya*; Matsuya, Yusuke; Kaida, Atsushi*; Nojima, Hitomi*; Furuta, Takuya; Sato, Kaoru; Yoshimura, Ryoichi*; Miura, Masahiko*
Journal of Radiation Research (Internet), 65(5), p.628 - 639, 2024/09
Times Cited Count：0 Percentile：0.00(Biology)In X-ray therapy, radiation regimen is planned to eliminate tumors while minimizing side effects on normal tissue. When irradiating the oral cavity, which includes dental metallic crowns, intense mucositis can occasionally be induced. However, the mechanism underlying the radiosensitization remains unclear. In this study, we investigated the radiosensitization mechanism using cell experiments and computational simulations. As a result, the enhancement ratio observed in the cell experiments was 1.2-1.4, which was found to be predominately attributed to local dose increase near metal. On the other hand, as a result of dose evaluation based on CT images as a preclinical test, it was found that the dose increase was underestimated due to the complex anatomical structure of the human body, and microscopic dose evaluation was necessary. This outcome contributes to the precise understanding of side effects on normal cells around metals.
Sato, Tatsuhiko; Matsuya, Yusuke; Hamada, Nobuyuki*
Journal of Radiation Research (Internet), 65(4), p.500 - 506, 2024/07
Times Cited Count：2 Percentile：62.68(Biology)We therefore evaluated the mean and uncertainty of relative biological effectiveness (RBE) for diseases of the circulatory system (DCS) by applying a microdosimetric kinetic model specialized for RBE estimation of tissue reactions. For this purpose, we analyzed several RBE data for DCS determined by past animal experiments and evaluated the radius of the subnuclear domain best fit to each experiment as a single free parameter included in the model. Our analysis suggested that RBE for DCS tends to be lower than that for skin reactions, and their difference was borderline significant due to large variances of the evaluated parameters. These findings will help determine RBE by ICRP for preventing tissue reactions.
Matsuya, Yusuke; Sato, Tatsuhiko; Kusumoto, Tamon*; Yachi, Yoshie*; Seino, Ryosuke*; Miwa, Misako*; Ishikawa, Masayori*; Matsuyama, Shigeo*; Fukunaga, Hisanori*
Scientific Reports (Internet), 14, p.16696_1 - 16696_14, 2024/07
Times Cited Count：2 Percentile：82.10(Multidisciplinary Sciences)Boron neutron capture therapy (BNCT) is a unique radiotherapy to selectively eradicate tumor cells using boron compounds (e.g., 4-borono-L-phenylalanine [BPA]) that are heterogeneously taken up at the cellular level. However, the impacts of tempo-spatial heterogenicity on cell killing remain unclear. With the technical combination of radiation track detector, cell cycle analysis, and biophysical simulations, we demonstrated the cell cycle-dependent heterogenicity of BPA uptake and following biological impacts of 
B(n, )
Li reactions in HeLa cells expressing Fluorescent Ubiquitination-based Cell Cycle Indicators (FUCCI), as well as its modification effects of polyvinyl alcohol (PVA). As a result, we revealed that the intracellular BPA concentration in the S/G2/M phase was higher than that in the G1/S phase and that PVA modified the cell cycle dependence. Further, these findings lead to the development of the first BPA-PVA-based model for predicting BNCT treatment effects. These outcomes may contribute to more precision of therapeutic efficacy, when BNCT is combined with PVA and/or cell cycle-specific anticancer agents.
Nojima, Hitomi*; Kaida, Atsushi*; Matsuya, Yusuke; Uo, Motohiro*; Yoshimura, Ryoichi*; Arazi, L.*; Miura, Masahiko*
Scientific Reports (Internet), 14, p.11468_1 - 11468_13, 2024/05
Times Cited Count：0 Percentile：0.00(Multidisciplinary Sciences)Diffusing alpha-emitters radiation therapy (Alpha-DaRT) is a unique radiotherapy that uses seeds emitting alpha particles placed in solid tumors to kill cancer cells surrounding the seeds. Although the DNA damage response is an important cellular response that determines cell death after radiation; however, how DNA damage response occurs during Alpha-DaRT treatment has not yet been explored. In this study, we measured the spatiotemporal characteristics of the DNA damage response, including the number of DNA double-strand breaks and G2 arrest, during Alpha-DaRT treatment by cell experiments using HeLa cells expressing the Fucci cell cycle visualization system. As a result, we found a strong correlation between the number of alpha particles detected by solid-state track detector CR-39 and 
-H2AX staining, a marker for detecting DNA damage, and that the area of G2-arrested cells spread over a wider area up to 24 hours. In addition, time-lapse observations revealed that cell cycle dynamics change depending on the distance from the seed. The experimental model in this study revealed for the first time the spatiotemporal information of the DNA damage response around the seed during Alpha-DaRT treatment.
Matsuya, Yusuke; Sato, Tatsuhiko; Yachi, Yoshie*; Date, Hiroyuki*; Hamada, Nobuyuki*
Scientific Reports (Internet), 14, p.12160_1 - 12160_14, 2024/05
Times Cited Count：2 Percentile：62.68(Multidisciplinary Sciences)Understand mechanisms of radiation cataracts that are of concern in the field of radiation protection and radiation therapy. However, biological effects in HLEC following protracted exposure have not yet fully been explored. Here, we investigated the temporal kinetics of DNA double-strand breaks (DSBs) and cell survival of HLEC after exposure to photon beams at various dose rates, compared to those of human lung fibroblasts (WI-38). In parallel, we quantified the recovery for DSB and cell survival using a biophysical model. The study revealed that HLEC cells have a lower repair rate than WI-38 cells. There is no significant impact of dose rate on cell survival in both cell lines in the dose-rate range of 0.033-1.82 Gy/min. On the other hand, the experimental residual DSBs showed inverse dose rate effects (IDREs) compared to the model prediction, highlighting the importance of the IDREs in evaluating radiation effects on the ocular lens.
Saga, Ryo*; Matsuya, Yusuke; Obara, Hideki*; Komai, Fumio*; Yoshino, Hironori*; Aoki, Masahiko*; Hosokawa, Yoichiro*
Advances in Radiation Oncology (Internet), 9(4), p.101437_1 - 101437_5, 2024/04
The curative effects after radiotherapy are evaluated by the index of tumor control probability (TCP), and the treatment regimen has been determined empirically based on clinical experiences. In recent years, in order to determine TCP for any treatment regimens based on cell experiments, it is necessary to consider the existence of radioresistant cancer stem cells, which are included in tumors at from a few to several tens of percent. Our previous study has proposed an integrated microdosimetric-kinetic (IMK) model that explicitly considers cancer stem cells, and successfully reproduced cancer cell death obtained from cell experiments and clinical TCP. However, the verification so far has been limited to comparison with the clinical data of Hirosaki University Hospital, and comparative verification with clinical data of other facilities has not been performed. In this study, we focused on the stereotactic radiotherapy against non-small cell lung cancer that prescribes a large dose at once, and compared the public data collected by meta-analysis with the IMK model. As a result, it was found that the IMK model considering cancer stem cells well reproduced the clinical TCP regardless of the observed facility type. This work would contribute to the development of technology for predicting curative effects of radiotherapy with high precision.
C ions based on first-principles calculationsSekikawa, Takuya; Matsuya, Yusuke; Hwang, B.*; Ishizaka, Masato*; Kawai, Hiroyuki*; Ono, Yoshiaki*; Sato, Tatsuhiko; Kai, Takeshi
Nuclear Instruments and Methods in Physics Research B, 548, p.165231_1 - 165231_6, 2024/03
Times Cited Count：1 Percentile：68.69(Instruments & Instrumentation)One of the main causes of radiation effects on the human body is thought to be damage to DNA, which carries genetic information. However, it is not fully understood what kind of molecular structural changes DNA undergoes upon radiation damage. Since it has been reported that various types of DNA damage are formed when DNA is irradiated, our group has investigated the relationship between DNA damage and various patterns of radiation-induced ionization induced by radiation. Although we have so far analyzed DNA damage in a simple system using a rigid body model of DNA, more detailed calculations are required to analyze the molecular structural changes in DNA, which are considered to be important in considering the effects on the human body. In this study, we attempted to clarify the molecular conformational changes of DNA using OpenMX, a first-principles calculation software that can discuss electronic states based on molecular structures. Specifically, we calculated the most stable structure, band dispersion, and wave function of DNA under the assumption that one and two electrons are ionized by various radiation. In the presentation, we will discuss the relationship between the energy dependence of each incident radiation type and the molecular conformational change of DNA. In addition, the radiation-induced changes in the basic physical properties of DNA (corresponding to the initial stage of DNA damage) will be discussed from the viewpoints of both radiation physics and solid state physics.
Hirata, Yuho; Kai, Takeshi; Ogawa, Tatsuhiko; Matsuya, Yusuke; Sato, Tatsuhiko
Nuclear Instruments and Methods in Physics Research B, 547, p.165183_1 - 165183_7, 2024/02
Times Cited Count：0 Percentile：0.00(Instruments & Instrumentation)The luminescence efficiency of the phosphors for swift ions is known to decrease because of the quenching effects. To obtain the precise dose distributions using phosphor detectors, understanding the mechanisms of quenching effects is mandatory. Here, we developed a new model for estimating the luminescence intensity of phosphors based on the track-structure modes for arbitrary materials implemented in PHITS. The developed model enabled the simulation of the quenching effects of the BaFBr detector and was verified by comparing the results to the corresponding measured data. The present model is expected to contribute to developing phosphor detectors worldwide.
Matsuya, Yusuke; Yoshii, Yuji*; Kusumoto, Tamon*; Akamatsu, Ken*; Hirata, Yuho; Sato, Tatsuhiko; Kai, Takeshi
Physics in Medicine & Biology, 69(3), p.035005_1 - 035005_12, 2024/02
Times Cited Count：2 Percentile：62.68(Engineering, Biomedical)Time-dependent yields of chemical products resulted in 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 allows to determine several atomic interactions such as ionizations and electronic excitations as physical stage. However, a chemical code for simulating products of water radiolysis does not exist in the PHITS package. Here, we developed a chemical simulation code dedicated for the PHITS code, hereafter called PHITS-Chem code, which enables calculating G values of water radiolysis species (OH radical, e
, H
, HO etc) by electron beams. The estimated G values during 1 
s are in agreement with the experimental ones and other simulations. This PHITS-Chem code enables simulating the dynamics in the presence of OH radical scavenger, and is useful for evaluating contributions of direct and indirect effects on DNA damage induction. This code will be included and be available in the future version of PHITS.
Sato, Tatsuhiko; Iwamoto, Yosuke; Hashimoto, Shintaro; Ogawa, Tatsuhiko; Furuta, Takuya; Abe, Shinichiro; Kai, Takeshi; Matsuya, Yusuke; Matsuda, Norihiro; Hirata, Yuho; et al.
Journal of Nuclear Science and Technology, 61(1), p.127 - 135, 2024/01
Times Cited Count：110 Percentile：99.97(Nuclear Science & Technology)The Particle and Heavy Ion Transport code System (PHITS) is a general-purpose Monte Carlo radiation transport code that can simulate the behavior of most particle species with energies up to 1 TeV (per nucleon for ions). Its new version, PHITS3.31, was recently developed and released to the public. In the new version, the compatibility with high-energy nuclear data libraries and the algorithm of the track-structure modes have been improved. In this paper, we summarize the upgraded features of PHITS3.31 with respect to the physics models, utility functions, and application software introduced since the release of PHITS3.02 in 2017.
Shiraishi, Yuta*; Matsuya, Yusuke; Kusumoto, Tamon*; Fukunaga, Hisanori*
Physics in Medicine & Biology, 69(1), p.015017_1 - 015017_14, 2024/01
Times Cited Count：4 Percentile：94.26(Engineering, Biomedical)FLASH radiotherapy (FLASH-RT) using ultra-high dose rate (
40 Gy/sec) is known as a new treatment which is expected to enable preserving normal tissue functions, compared to the conventional radiotherapy (CONV-RT) with high dose rate (
6 Gy/min). To date, it is believed that the modulation of chemical processes caused by interactions between radiation tracks under FLASH-RT is a key factor in the functional preservation of normal tissues; however, the relationship between changes in chemical processes and cellular responses remains uncertain. In this study, we developed a prediction model (integrated microdosimetric-kinetic (IMK) model for FLASH-RT) taking into account of the relationship between the chemical process and the DNA damage yields (which is the initial response) under ultra-high dose rate irradiation, to investigate the cellular mechanisms. As a result, the developed model considering the chemical-processes dependent change in DNA damage yields successfully reproduced the measured cell-killing effects of both CONV-RT and FLASH-RT for various cell line types. This model development would contribute on not only precisely understanding of cellular mechanisms after FLASH-RT irradiation but also enabling the prediction of therapeutic effects with high precision.
Kai, Takeshi; Toigawa, Tomohiro; Matsuya, Yusuke; Hirata, Yuho; Tezuka, Tomoya*; Tsuchida, Hidetsugu*; Yokoya, Akinari*
RSC Advances (Internet), 13(46), p.32371 - 32380, 2023/11
Times Cited Count：3 Percentile：26.32(Chemistry, Multidisciplinary)Although scientific knowledge of photolysis and radiolysis of water is widely used in the life sciences and other fields, the formation mechanism of the spatial distribution of hydrated electrons (spur) resulting from energy deposition to water is still not well understood. The chemical reaction times of hydrated electrons, OH radicals, and H
O
in the spur strongly depend on the spur radius. In our previous study, we elucidated the mechanism at a specific given energy (12.4 eV) by first-principles calculations. In the present study, we performed first-principles calculations of the spur radius at the deposition energies of 11-19 eV. The calculated spur radius is 3-10 nm, which is consistent with the experimental prediction (~4 nm) for the energy range of 8-12.4 eV, and the spur radius gradually increases with increasing energy. The spur radius is a new scientific knowledge and is expected to be widely used for estimating radiation DNA damage.
