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

Kai, Takeshi; Yokoya, Akinari*; Ukai, Masatoshi*; Fujii, Kentaro*; Toigawa, Tomohiro; Watanabe, Ritsuko*

Physical Chemistry Chemical Physics, 20(4), p.2838 - 2844, 2018/01

https://doi.org/10.1039/C7CP06903K

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.

Dynamic behavior of secondary electrons produced by a high-energy electron in liquid water

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.

Dynamic behavior of secondary electrons in liquid water at the earliest stage upon irradiation; Implications for DNA damage localization mechanism

Kai, Takeshi; Yokoya, Akinari*; Ukai, Masatoshi*; Fujii, Kentaro*; Watanabe, Ritsuko*

Journal of Physical Chemistry A, 120(42), p.8228 - 8233, 2016/10

https://doi.org/10.1021/acs.jpca.6b05929

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.

Ultraviolet circular dichroism spectroscopy for protein structural study

Izumi, Yudai; Yamamoto, Satoshi*; Fujii, Kentaro; Yokoya, Akinari

Hoshasen Seibutsu Kenkyu, 51(1), p.91 - 106, 2016/03

no abstracts in English

Recent progress of radiation physicochemical process (second part)

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.

Investigation of the fragmentation of core-ionised deoxyribose; A Study as a function of the tautomeric form

Herv du Penhoat, M.-A.*; Kamol Ghose, K.*; Gaigeot, M.-P.*; Vuilleumier, R.*; Fujii, Kentaro; Yokoya, Akinari; Politis, M.-F.*

Physical Chemistry Chemical Physics, 17(48), p.32375 - 32383, 2015/12

https://doi.org/10.1039/C5CP05196G

Thermal equilibrium and prehydration processes of electrons injected into liquid water calculated by dynamic Monte Carlo method

Kai, Takeshi; Yokoya, Akinari; Ukai, Masatoshi*; Fujii, Kentaro; Watanabe, Ritsuko

Radiation Physics and Chemistry, 115, p.1 - 5, 2015/10

https://doi.org/10.1016/j.radphyschem.2015.05.021

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.

Live-cell imaging study of mitochondrial morphology in mammalian cells exposed to X-rays

Noguchi, Miho; Kanari, Yukiko; Yokoya, Akinari; Narita, Ayumi; Fujii, Kentaro

Radiation Protection Dosimetry, 166(1-4), p.101 - 103, 2015/09

https://doi.org/10.1093/rpd/ncv157

Real-time observation of irradiated HeLa-cell modified by fluorescent ubiquitination-based cell-cycle indicator using synchrotron X-ray microbeam

Narita, Ayumi; Kaminaga, Kiichi; Yokoya, Akinari; Noguchi, Miho; Kobayashi, Katsumi*; Usami, Noriko*; Fujii, Kentaro

Radiation Protection Dosimetry, 166(1-4), p.192 - 196, 2015/09

https://doi.org/10.1093/rpd/ncv156

For the knowledge about irradiation effects of mammalian cells depending on the cell cycle, most of them had been analyzed by statistical approches. Our purpose is to establish the method for real-time observation of irradiated cells under a microscope. Fluorescent ubiquitination-based cell cycle indicator (FUCCI) human cancer (HeLa) cells (red indicates G1; green, S/G2) were exposed to a synchrotron X-ray microbeam. Cells in either G1 or S/G2 were selectively irradiated according to cell color observed in the same microscopic field in a culture dish. Time-lapse micrographs of the irradiated cells were acquired for 24 h after irradiation. The cell cycle was strongly arrested by irradiation at S/G2 and never progressed to G1. In contrast, cells irradiated at G1 progress to S/G2 with a similar time course as non-irradiated control cells. These results show single FUCCI cell exposure and live cell imaging are powerful methods for studying radiation effects on the cell cycle.

Cross sections, stopping powers, and energy loss rates for rotational and phonon excitation processes in liquid water by electron impact

Kai, Takeshi; Yokoya, Akinari; Ukai, Masatoshi*; Watanabe, Ritsuko

Radiation Physics and Chemistry, 108, p.13 - 17, 2015/03

https://doi.org/10.1016/j.radphyschem.2014.11.008

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.