Kai, Takeshi; Yokoya, Akinari*; Fujii, Kentaro*; Watanabe, Ritsuko*
Hoshasen Kagaku (Internet), (106), p.21 - 29, 2018/11
It is thought to that the biological effects such as cell death or mutation are induced by complex DNA damage which are formed by several damage sites within a few nm. As the prediction of complex DNA damage at an electron track end, we report our outcomes. These results indicate that DNA damage sites comprising multiple nucleobase lesions with a single strand breaks can be formed by multiple collisions of the electrons within 1 nm. This multiple damage site cannot be processed by base excision repair enzymes. Pre-hydrated electrons can also be produced resulting in an additional base lesion over a few nm from the multi-damage site. This clustered damage site may be finally converted into a double strand break. These DSBs include another base lesion(s) at their termini that escape from the base excision process and which may result in biological effect. Our simulation is useful to reveal phenomena involved in radiation physico-chemistry as well as the DNA damage prediction.
Kai, Takeshi; Yokoya, Akinari*; Ukai, Masatoshi*; Fujii, Kentaro*; Toigawa, Tomohiro; Watanabe, Ritsuko*
Physical Chemistry Chemical Physics, 20(4), p.2838 - 2844, 2018/01
It is thought that complex DNA damage which induces in radiation biological effects is formed at radiation track end. Thus, the earliest stage of water radiolysis at the electron track end was studied to predict DNA damage. These results indicate that DNA damage sites comprising multiple nucleobase lesions with a single strand breaks can therefore be formed by multiple collisions of the electrons within three base pairs (3bp) of a DNA strand. This multiple damage site cannot be processed by base excision repair enzymes. However, pre-hydrated electrons can also be produced resulting in an additional base lesion more than 3bp away from the multi-damage site. This clustered damage site may be finally converted into a double strand break (DSB) when base excision enzymes process the additional base lesions. These DSBs include another base lesion(s) at their termini that escape from the base excision process and which may result in biological effects such as mutation in surviving cells.
Watanabe, Ritsuko*; Kai, Takeshi; Hattori, Yuya*
Radioisotopes, 66(11), p.525 - 530, 2017/11
To understand the mechanisms of radiation biological effects, modeling and simulation studies are important. In particular, simulation approach is powerful tool to evaluate modeling of mechanisms and the relationship among experimental results in different spatial scale of biological systems such as DNA molecular and cell. This article summarizes our approach to evaluate radiation action on DNA and cells by combination of knowledge in radiation physics, chemistry and biology. It contains newly theoretical approach to estimate physico-chemical process of DNA damage induction in addition to typical method of DNA damage prediction. Outline of the mathematical model for dynamics of DNA damage and cellular response is also presented.
Kai, Takeshi; Yokoya, Akinari*; Fujii, Kentaro*; Watanabe, Ritsuko*
Yodenshi Kagaku, (8), p.11 - 17, 2017/03
It is thought to that the biological effects such as cell death or mutation are induced by complex DNA damage which are formed by several damage sites within a few nm. We calculated dynamic behavior of secondary electrons produced by primary electron and positon of high energy in water whose composition ratio is similar to biological context. The secondary electrons induce the ionization or electronic excitation near the parent cations. The decelerated electrons about 10% are distributed to their parent cations by the attractive Coulombic force. From the results, we predicted the following formation mechanism for the complex DNA damage. The electrons ejected from DNA could induce the ionization or the electronic excitation within the DNA. The electrons attracted by the Coulombic force are pre-hydrated in water layer of the DNA. The pre-hydrated electrons could induce to the DNA damage by dissociative electron transfer. As the results, the complex DNA damage with 1 nm could be formed by the interaction of not only the primary electron or positon but also the secondary electrons.
Watanabe, Ritsuko; Hattori, Yuya; Kai, Takeshi
International Journal of Radiation Biology, 92(11), p.660 - 664, 2016/11
To understand the effect of internal exposure of Cs, we focus on estimation of microscopic energy deposition pattern and DNA damage induced by directly emitted electrons (beta-rays, internal conversion electrons, Auger electrons) from Cs. Monte Carlo track simulation method was used to calculate the microscopic energy deposition pattern. To simulate the energy deposition by directly emitted electrons, we considered the multiple ejections of electrons after internal conversion. Induction process of DNA strand breaks and base lesions was modeled and simulated using Monte Carlo methods for cell mimetic condition. The yield and spatial distribution of simple and complex DNA damage were calculated for the cases of -rays and electrons from Cs. The simulation showed that significant difference of DNA damage spectrum was not caused by the difference between secondary electron spectrum by -rays and directly ejected electron spectrum. The result support that the existing evaluation that internal exposure and external exposure are almost equivalent.
Kai, Takeshi; Yokoya, Akinari; Ukai, Masatoshi; Fujii, Kentaro; Watanabe, Ritsuko
International Journal of Radiation Biology, 92(11), p.654 - 659, 2016/11
Kai, Takeshi; Yokoya, Akinari*; Ukai, Masatoshi*; Fujii, Kentaro*; Watanabe, Ritsuko*
Journal of Physical Chemistry A, 120(42), p.8228 - 8233, 2016/10
Low energy secondary electrons produced by an ionizing radiation in a living cell may involve in formation of complexed DNA damage. We performed theoretical study for numerical calculation of dynamic behavior of the electrons to imply a formation of radiation damage to DNA. The decelerating electrons are gradually attracted to their parent cations by the Coulombic force within hundreds of fs, and about 12.6 % of electrons are finally distributed within 2 nm from the cations. The collision fraction of the ionization and excitation within 1 nm from the cation was estimated to be about 40 %. From those analyses, we suggested a process of DNA damage that the secondary electrons may cause highly localized lesions around a cation in DNA molecule through additional dissociative electron transfer as well as the ionization or the excitation if the electrons are ejected from DNA. The localized damage may involve ultimately in biological effects such as cell death or mutation induction.
Kai, Takeshi; Yokoya, Akinari; Fujii, Kentaro; Watanabe, Ritsuko
Hoshasen Kagaku (Internet), (101), p.3 - 11, 2016/04
Behavior analysis of low energy electrons in liquid water provides the fundamentals for successive radiation chemistry, and it makes analysis of DNA damage implication involved in the electrons possible. We have progressed theoretical studies for radiation physicochemical process of liquid water to clear the role of low-energy secondary electrons damage to DNA. The process has included many unknown factors for the DNA damage so far. Based on the results, we implied a newly formation process of unrepair DNA damage produced by the secondary electrons assumed that it was ejected from DNA by impact of a high energy electron. We report our outcomes separately in three manuscripts entitled "Recent progress of radiation physicochemical process (first, second, third parts)" to journal of radiation chemistry. In this first part, we outline recent status of studies for the DNA damage and the radiation physicochemical process, we also show calculation method of electron impact cross sections involved strongly in electron deceleration in liquid water in the topics of our outcomes. From the calculated results, we also report our prediction, which are different from previous one, for electron thermalization.
Kai, Takeshi; Yokoya, Akinari*; Fujii, Kentaro*; Watanabe, Ritsuko*
Hoshasen Kagaku (Internet), (102), p.49 - 56, 2016/00
Behavior analysis of low energy electrons in liquid water provides the fundamentals for successive radiation chemistry, and it makes analysis of DNA damage implication involved in the electrons possible. We have progressed theoretical studies for radiation physicochemical process of water to clear the role of secondary electrons damage to DNA. The process has included many unknown factors for the DNA damage so far. We implied a newly formation process of unrepair DNA damage produced by the secondary electrons. We report our outcomes separately in three manuscripts entitled "Recent progress of radiation physicochemical process (first, second, third parts)". In this second part, we show calculated results of thermalization lengths and times of electrons in water to verify a dynamic Monte Carlo code developed in this study. From the calculated results, we also report our prediction, which are different from previous one, for thermalization and pre-hydration processes.
Hattori, Yuya; Yokoya, Akinari; Watanabe, Ritsuko
BMC Systems Biology (Internet), 9, p.90_1 - 90_22, 2015/12
The radiation-induced bystander effect is a biological response observed in non-irradiated cells surrounding an irradiated cell, which is known to be caused by two intercellular signaling pathways. However, the behavior of the signals is largely unknown. To investigate the role of these signaling pathways, we developed a mathematical model to describe the cellular response to direct irradiation and the bystander effect, with a particular focus on cell-cycle modification. The analysis of model dynamics revealed that bystander effect on cell cycle modification was different between low-dose irradiation and high-dose irradiation. We demonstrated that signaling through both pathways induced cell cycle modification via the bystander effect. By simulating various special and temporal conditions of irradiation and cell characteristics, our model will be a powerful tool for the analysis of the bystander effect.
Kai, Takeshi; Yokoya, Akinari; Ukai, Masatoshi*; Fujii, Kentaro; Watanabe, Ritsuko
Radiation Physics and Chemistry, 115, p.1 - 5, 2015/10
Role of secondary electrons on DNA damage have not been understood sufficiently because there still exists a lack of study for thermalization process of an electron in liquid phase. We calculated thermalization lengths and spatial distributions of an electron in liquid water using cross sections for rotation and phonon excitations in a liquid phase. Obtained thermalization lengths are in good agreement with experimental results reported by literatures. Thermalization time was also estimated from time evolution of spatial distributions of the incident electron to be hundreds femtoseconds. From these results, we predict that thermalization and pre-hydration of electron might progress simultaneously. These electrons possibly cause damage in biological molecules in a cell. Particularly severe types of DNA damage consisting of proximately located multiple lesions are potentially induced by reaction of DNA with the thermalized electrons by dissociative electron transfer.
Hattori, Yuya; Suzuki, Michiyo; Funayama, Tomoo; Kobayashi, Yasuhiko; Yokoya, Akinari; Watanabe, Ritsuko
Radiation Protection Dosimetry, 166(1-4), p.142 - 147, 2015/09
Cell-to-cell communication is one of the important factors to understand the mechanisms of radiation-induced responses such as radiation-induced bystander effects at low doses. In the present study, we propose simulation-based analyses of the intercellular signal transmissions between the individual cells in the cellular population. We developed the transmissions of two types of signals, i.e., X is transmitted via culture medium and Y is transmitted via gap junctions based on the diffusion equation. To observe the cell cycle as the response of cell induced by the signals, X and Y, we represented the cell cycle as a virtual clock including several check-point pathways and the cyclic process (G1, S, G2, M phases). The cellular population was divided into the grids (cells), and the signals and the clock were calculated for each grid. The signals, X, Y, were transmitted to the cells and stopped the clocks at the check points. Furthermore, the radiation was modeled as the radiation signal, Z, which affected the clock and the signals, X and Y. We input the radiation signal, Z, to specific cells, and simulated the behaviors of the clock of each cell and signals, X and Y. We will discuss the usefulness of our model for investigating the mechanisms of radiation-induced responses of the cell cycle via cell-to-cell communications.
Watanabe, Ritsuko; Rahmanian, S.*; Nikjoo, H.*
Radiation Research, 183(5), p.525 - 540, 2015/05
To calculate the spectrum of initial base damage induced by selected electrons and ions, Monte Carlo track structure method was used to simulate the radiation induced DNA damage in a cell mimetic condition based on a single track action. We present relative yield of strand breaks and base damage for selected monoenergetic electrons 100 eV - 100 keV, photons C, Al and Ti; and some selected ions (3.2 MeV/u proton; 0.74 and 2.4 MeV/u He; 29 MeV/u N, and 950 MeV/u Fe). Data are presented for simple and complex types of DNA damage. The ratios of yields of base damage to SSBs were estimated to be about 2-4 independent on the LETs examined. The contribution of base damage to the complexity of damage site was shown to be significant. The data can be used for testing mechanistic models of DNA repair kinetics and in particular the base excision repair.
Kai, Takeshi; Yokoya, Akinari; Ukai, Masatoshi*; Watanabe, Ritsuko
Radiation Physics and Chemistry, 108, p.13 - 17, 2015/03
Role of secondary electrons on DNA damage have not been understood sufficiently because there still exists a lack of cross section of rotational and phonon excitation in the liquid phase for precise simulation of the electron behavior. We calculated cross sections, stopping powers, and energy loss rates for the excitations in liquid water. The values for rotation are less by three orders of magnitude than those in the gas phase, while the values for phonon are close to those reported for amorphous ice. Thermalization process has so far been estimated from an assumption that the energy loss rates do not depend strongly on the energy below 1 eV. However, we found that the energy loss rates depend significantly on the energy. This fact indicates that the thermalization time will be longer than the previously estimated time, and we predict that thermalization process strongly involve in subsequent hydrated and chemical processes. The data set provide here is expected to useful to make the role of the secondary electrons on DNA damage much clear.
Tsuda, Shuichi; Sato, Tatsuhiko; Watanabe, Ritsuko; Takada, Masashi*
Journal of Radiation Research, 56(1), p.197 - 204, 2015/01
Radial dependence of lineal energy distribution, yf(y), have been experimentally evaluated for a 0.72 micrometer site in tissue using 290 MeV/u carbon and 500 MeV/u iron ion beams using a wall-less tissue equivalent proportional counter. The yf(y) distributions and dose-mean of y, are compared with the calculation by a track structure simulation code TRACION and a microdosimetric function of the PHITS code. The values of the measured agree with those of the calculation within 20% but differences in the shape of yf(y) were found in the case of the iron ion irradiation. The result indicates that further improvement of the calculation model for yf(y) distribution in PHITS is needed in terms of the analytical function that reproduce energy deposition by delta rays, in the case that primary ions have LET more than a few hundred keV/micrometer.
Kai, Takeshi; Yokoya, Akinari; Ukai, Masatoshi*; Fujii, Kentaro; Higuchi, Mariko; Watanabe, Ritsuko
Radiation Physics and Chemistry, 102, p.16 - 22, 2014/09
no abstracts in English
Shiina, Takuya*; Watanabe, Ritsuko; Suzuki, Masao*; Yokoya, Akinari
Journal of Radiation Research, 55(Suppl.1), p.i15 - i16, 2014/03
Yokoya, Akinari; Ukai, Masatoshi*; Oka, Toshitaka*; Kai, Takeshi; Watanabe, Ritsuko; Fujii, Kentaro
Shototsu, 11(2), p.33 - 39, 2014/03
no abstracts in English
Nakajima, Nakako*; Brunton, H.*; Watanabe, Ritsuko; Shrikhande, A.*; Hirayama, Ryoichi*; Matsufuji, Naruhiro*; Fujimori, Akira*; Murakami, Takeshi*; Okayasu, Ryuichi*; Jeggo, P.*; et al.
PLOS ONE (Internet), 8(8), p.e70107_1 - e70107_14, 2013/08
Heavy particle irradiation can produce complex DNA double strand breaks (DSBs) within the particle trajectory. Additionally, secondary electrons, termed delta-electrons, can create low linear energy transfer (LET) damage distant from the track. Using imaging with deconvolution, we show that at 8 hours after exposure to Fe ions, H2AX foci forming at DSBs within the particle track are large and encompass multiple smaller and closely localised foci, which we designate as clustered H2AX foci. We also identified simple H2AX foci distant from the track. They are rapidly repaired. Clustered H2AX foci induced by heavy particle radiation cause prolonged checkpoint arrest compared to simple H2AX foci. However, mitotic entry was observed when 10 clustered foci remain. Thus, cells can progress into mitosis with multiple clusters of DSBs following the traversal of a heavy particle.
Shiina, Takuya; Watanabe, Ritsuko; Shiraishi, Iyo; Suzuki, Masao*; Sugaya, Yuki; Fujii, Kentaro; Yokoya, Akinari
Radiation and Environmental Biophysics, 52(1), p.99 - 112, 2013/03