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Journal Articles

Analysis of the high-dose-range radioresistance of prostate cancer cells, including cancer stem cells, based on a stochastic model

Saga, Ryo*; Matsuya, Yusuke; Takahashi, Rei*; Hasegawa, Kazuki*; Date, Hiroyuki*; Hosokawa, Yoichiro*

Journal of Radiation Research, 60(3), p.298 - 307, 2019/05

In radiotherapy, it is recognized that cancer stem cells (CSCs) in tumor tissue shows radio-resistance. However, the relationship between content percentage of the CSCs and dose-response curve on cell survival remain unclear. In this study, we developed a stochastic model considering progeny cells and stem cells, and investigated the impact of stem cells on radio-sensitivity. From the flow-cytometric analysis (cell experiments), the content percentage of stem cells was 3.2% or less which agreed well with the model estimation from the cell survival curve. Based on the verification, it is suggested that cell survival in high-dose range is largely affected by the CSCs. In addition, regarding the sub-population of stem cells, the present model well reproduces the dose response on lethal lesions to DNA comparing with the conventional LQ model. This outcome indicates that the stem cells must be considered for describing the dose-response curve in wide dose range.

Journal Articles

Recent progress of radiation physicochemical process (third part)

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.

Journal Articles

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

 Times Cited Count:2 Percentile:37.68(Chemistry, Physical)

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.

Journal Articles

Modern radiation chemistry (Applications), 16; Computer simulation study of initial process of radiation biological effect

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.

Journal Articles

Reactivity of an antioxidant, edaravone, with reactive oxygen species and its chemical repair properties against oxidative damage on DNA

Hata, Kuniki; Lin, M.*; Yokoya, Akinari*; Fujii, Kentaro*; Yamashita, Shinichi*; Muroya, Yusa*; Katsumura, Yosuke*

Hoshasen Kagaku (Internet), (103), p.29 - 34, 2017/04

Reactivity of edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one), which is known to show high antioxidative properties, with oxidative species, such as hydroxyl radical ($${}^{bullet}$$OH) and azide radical (N$$^{bullet}$$$$_{3}$$), was investigated by a pulse radiolysis experiment, and generation behavior of edaravone radicals produced through these reactions were observed. It was shown that OH-adducts are produced by the reaction with $${}^{bullet}$$OH in contrast to the other oxidative radicals, which react with edaravone by an electron transfer reaction. Chemical repair properties of edaravone against DNA lesions produced by reactions of DNA with oxidative species were also investigated by a pulse radiolysis experiment with deoxyguanosine monophosphate (dGMP) and a $$gamma$$-radiolysis experiment with plasmid DNA solutions. It was observed that edaravone reduced dGMP radicals just after produced in a dilute aqueous solution and inhibited some base lesions on plasmid DNA more effectively than single strand breaks. These results show that edaravone may protect living system from oxidative stress, such as radiation, by not only scavenging oxidative species but also reducing precursors of DNA leisons.

Journal Articles

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.

Journal Articles

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

Journal Articles

Cellular automaton-based model for radiation-induced bystander effects

Hattori, Yuya; Yokoya, Akinari; Watanabe, Ritsuko

BMC Systems Biology (Internet), 9, p.90_1 - 90_22, 2015/12

 Times Cited Count:8 Percentile:37.35(Mathematical & Computational Biology)

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.

Journal Articles

Secondary structure alterations of histones H2A and H2B in X-irradiated human cancer cells; Altered histones persist in cells for at least 24 hours

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

Radiation Research, 184(5), p.554 - 558, 2015/11

 Times Cited Count:4 Percentile:59.33(Biology)

Journal Articles

Localization estimation of ionizing radiation-induced abasic sites in DNA in the solid state using fluorescence resonance energy transfer

Akamatsu, Ken; Shikazono, Naoya; Saito, Takeshi*

Radiation Research, 183(1), p.105 - 113, 2015/01

 Times Cited Count:12 Percentile:25.01(Biology)

Clustered DNA damage is considered an important factor in determining the biological consequences of ionizing radiation. We here succeeded in estimating the localization of abasic sites (APs) in DNA irradiated with ionizing radiation using fluorescence resonance energy transfer (FRET) without any involvement of repair enzyme functions. A linearized plasmid was irradiated with $$^{60}$$Co $$gamma$$-rays, the $$^{4}$$He$$^{2+}$$ beam, and the $$^{12}$$C$$^{5+}$$ beam in the solid state. A donor or acceptor fluorescent probe with a nucleophilic O-amino group was used to label APs. The results showed that the $$^{12}$$C$$^{5+}$$ beam likely produced close APs within a track. On the other hand, E values of $$^{60}$$Co $$gamma$$-rays and the $$^{4}$$He$$^{2+}$$ beam were less than those of the $$^{12}$$C$$^{5+}$$ beam, increased with increasing AP density, and were slightly greater than those of randomly distributed APs.

Journal Articles

Induction of genetic instability by transfer of a UV-A-irradiated chromosome

Urushibara, Ayumi*; Kodama, Seiji*; Yokoya, Akinari

Mutation Research; Genetic Toxicology And Environmental Mutagenesis, 766, p.29 - 34, 2014/05

 Times Cited Count:2 Percentile:86.93(Biotechnology & Applied Microbiology)

Journal Articles

Characterization of pathways dependent on the ${it uvsE}$, ${it uvrA1}$ or ${it uvrA2}$ gene product for UV resistance in ${it Deinococcus radiodurans}$

Tanaka, Masashi*; Narumi, Issei; Funayama, Tomoo; Kikuchi, Masahiro; Watanabe, Hiroshi*; Matsunaga, Tsukasa*; Nikaido, Osamu*; Yamamoto, Kazuo*

Journal of Bacteriology, 187(11), p.3693 - 3697, 2005/06

 Times Cited Count:28 Percentile:50.15(Microbiology)

no abstracts in English

Journal Articles

Roles of arabidopsis ${it AtREV1}$ and ${it AtREV7}$ in translation synthesis

Takahashi, Shinya; Sakamoto, Ayako; Sato, Shusei*; Kato, Tomohiko*; Tabata, Satoshi*; Tanaka, Atsushi

Plant Physiology, 138(2), p.870 - 881, 2005/06

 Times Cited Count:41 Percentile:25.71(Plant Sciences)

The error-prone DNA translation synthesis (error-prone TLS) has been well characterized in yeast and mammalians, but not in higher plants. Recent finding of an ${it AtREV3}$-disrupted mutant (${it rev3}$) in Arabidopsis suggested that the error-prone TLS is significant for tolerance to DNA damages in higher plant. To clarify the details of the error-prone TLS in higher plants, we analyzed the T-DNA inserted Arabidopsis mutants defective in ${it AtREV1}$ or ${it AtREV7}$ genes, which are thought to be involved in the error-prone TLS system. The ${it AtREV1}$ mutant (${it rev1}$) was sensitive to UV-B and cisplatin. The ${it AtREV7}$ mutant (${it rev7}$) was sensitive to long-term UV-B and cisplatin. These results suggest TLS mechanism exists in a higher plant and show that ${it AtREV1}$ and ${it AtREV7}$ have important roles in tolerating exposure to DNA-damaging agents, but their function might be redundant.

Journal Articles

"$$In situ$$" observation of guanine radicals induced by ultrasoft X-ray irradiation around the K-edge regions of nitrogen and oxygen

Yokoya, Akinari; Akamatsu, Ken; Fujii, Kentaro; Ukai, Masatoshi*

International Journal of Radiation Biology, 80(11-12), p.833 - 839, 2004/12

 Times Cited Count:7 Percentile:49.82(Biology)

no abstracts in English

Journal Articles

Decomposition of 2-deoxy-$$D$$-ribose by irradiation with 0.6 keV electrons and by 0.5 keV ultrasoft X-rays

Fujii, Kentaro; Akamatsu, Ken; Yokoya, Akinari

International Journal of Radiation Biology, 80(11-12), p.909 - 914, 2004/11

 Times Cited Count:9 Percentile:41.7(Biology)

no abstracts in English

Journal Articles

DNA strand breaks by direct energy deposition by Auger and photo-electrons ejected from DNA constituent atoms following K-shell photoabsorption

Watanabe, Ritsuko; Yokoya, Akinari; Fujii, Kentaro; Saito, Kimiaki

International Journal of Radiation Biology, 80(11-12), p.823 - 832, 2004/11

 Times Cited Count:13 Percentile:30.28(Biology)

no abstracts in English

Journal Articles

Useful tool for humam life and industry, 4; Ion beam applications

Yokota, Wataru

Kigyo Sapoto Gumma, P. 12, 2004/07

no abstracts in English

Journal Articles

PprI: A General switch responsible for extreme radioresistance of ${it Deinococcus radiodurans}$

Hua, Y.*; Narumi, Issei; Gao, G.*; Tian, B.*; Sato, Katsuya; Kitayama, Shigeru; Shen, B.*

Biochemical and Biophysical Research Communications, 306(2), p.354 - 360, 2003/06

 Times Cited Count:127 Percentile:4.15

We have identified a unique deinococcal gene, ${it pprI}$, as a general switch for downstream DNA repair and protection pathways, from a natural mutant, in which ${it pprI}$ is disrupted by a transposon. Complete functional disruption of the gene in wild-type leads to dramatic sensitivity to ionizing radiation. Radioresistance of the disruptant could be fully restored by complementation with ${it pprI}$. In response to radiation stress, PprI can significantly and specifically induce the gene expression of ${it recA}$ and ${it pprA}$ and enhance the enzyme activities of catalases. These results strongly suggest that PprI plays a crucial role in regulating multiple DNA repair and protection pathways in response to radiation stress.

Journal Articles

Spectroscopic study of site selective DNA damage induced by intense soft X-rays

Fujii, Kentaro

Hoshako, 16(3), p.151 - 158, 2003/05

no abstracts in English

Journal Articles

Detection of DNA damage induced by heavy ion irradiation in the individual cells with comet assay

Wada, Seiichi; Natsuhori, Masahiro*; Ito, Nobuhiko*; Funayama, Tomoo; Kobayashi, Yasuhiko

Nuclear Instruments and Methods in Physics Research B, 206, p.553 - 556, 2003/05

 Times Cited Count:3 Percentile:69.42

Determining the biological effects of a very low number of charged particles crossing the cell nucleus is interest for estimating the risk due to environmental exposure to charged particles. Especially it is necessary to detect the radiation damage induced by a precise number of charged particles in the individual cells. To compare the number of ions traversing the cell and the DNA damage produced by the hit ions, we applied comet assay. Cells attached on the ion track detector CR-39 were irradiated with 17.3 MeV/u 12C, 15.7 MeV/u, 10.4 MeV/u 20Ne and 6.9 MeV/u 40Ar ion beams at TIARA, JAERI-Takasaki. After irradiation, CR-39 was covered with 1 % agarose. After electrophoresis the CR-39 was taken off from the slide glass. The agarose gel on the CR-39 was stained with ethidium bromide and the opposite side of the CR-39 was etched with KOH-ethanol solution at 37 $$^{circ}C$$. We observed that the ion particles with higher LET value induced the heavier DNA damage, even by the same number of ion-hits within the irradiated cells.

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