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Yokota, Yuichiro; Funayama, Tomoo; Ikeda, Hiroko; Sakashita, Tetsuya; Suzuki, Michiyo; Kobayashi, Yasuhiko
JAEA-Review 2015-022, JAEA Takasaki Annual Report 2014, P. 67, 2016/02
The role of nitric oxide (NO) in bystander effect was investigated. Human fibroblasts were irradiated with 
-rays (LET: 0.2 keV/
m) or carbon-ion beam (108 keV/m), and then, co-cultured with the non-irradiated cells. After 24 h culture, the survival rates of non-irradiated cells and the concentrations of nitrate, an oxide of NO, in the medium were measured. The survival rates of non-irradiated cells decreased in dose-dependent and radiation quality-independent manners. Negative relationships between survival rates and nitrite concentrations existed, indicating the amounts of produced NO are an important determinant of bystander effects. Next, a reagent producing two molecules of NO in a half-life of 100 min was added in the culture medium. After incubation of 24 h the survival rates of treated cells did not decrease, suggesting NO produced intracellularly has an important role to lead the bystander effect but is not the signal molecule for intercellular communication.
Hattori, Yuya; Suzuki, Michiyo; Funayama, Tomoo; Kobayashi, Yasuhiko; Yokoya, Akinari; Watanabe, Ritsuko
Radiation Protection Dosimetry, 166(1-4), p.142 - 147, 2015/09
Times Cited Count：5 Percentile：37.04(Environmental Sciences)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.
Funayama, Tomoo; Yokota, Yuichiro; Suzuki, Michiyo; Sakashita, Tetsuya; Kobayashi, Yasuhiko
JAEA-Review 2014-050, JAEA Takasaki Annual Report 2013, P. 73, 2015/03
Using a collimating heavy-ion microbeam system, we have explored various effects of heavy-ion hit on biological materials. However, there are limitations of the collimating system in the size of the microbeam spot and in the irradiation speed that cannot be overcome in principle. Thus, we started the development of a focusing microbeam system for target-irradiating individual cells more precisely. In this year, we established the protocol for irradiating "actual" cell sample with scanned beam. In the experiment, the HeLa cells were inoculated on a CR-39 film, then place on the sample stage. The microscopic image of cells was analyzed, and the cells were irradiated with scanned neon microbeam. After irradiation, we found the correspondence of the distribution pattern of the ion hit positions and the -H2AX foci on cell nuclei, indicating rapid and accurate irradiation of individual cells with the focusing heavy-ion microbeam.
Suzuki, Michiyo; Hattori, Yuya; Sakashita, Tetsuya; Funayama, Tomoo; Yokota, Yuichiro; Ikeda, Hiroko; Kobayashi, Yasuhiko
JAEA-Review 2014-050, JAEA Takasaki Annual Report 2013, P. 88, 2015/03
Matsumoto, Hideki*; Tomita, Masanori*; Otsuka, Kensuke*; Hatashita, Masanori*; Maeda, Munetoshi*; Funayama, Tomoo; Yokota, Yuichiro; Suzuki, Michiyo; Sakashita, Tetsuya; Ikeda, Hiroko; et al.
JAEA-Review 2014-050, JAEA Takasaki Annual Report 2013, P. 76, 2015/03
The objective of this project is to elucidate molecular mechanisms for the induction of radioadaptive response through radiation-induced bystander responses induced by irradiation with heavy ion microbeams in JAEA. We found that the adaptive response was induced by Ar (520 MeV 
Ar
) microbeam-irradiation of a limited number of cells, followed by the broad beam-irradiation and that the adaptive response was almost completely suppressed by the addition of carboxy-PTIO, as a nitric oxide (NO) scavenger. In addition, we found several genes induced specifically and preferentially when radioadaptive response could be induced. We confirmed that 
expression was specifically induced only when radioadaptive response could be induced. Our findings strongly suggested that radioadaptive response can be induced by NO-mediated bystander responses evoked by irradiation with heavy ion microbeams.
mutants to microbeam irradiationSakashita, Tetsuya; Suzuki, Michiyo; Hattori, Yuya; Ikeda, Hiroko; Muto, Yasuko*; Yokota, Yuichiro; Funayama, Tomoo; Hamada, Nobuyuki*; Shirai, Kana*; Kobayashi, Yasuhiko
JAEA-Review 2014-050, JAEA Takasaki Annual Report 2013, P. 74, 2015/03
An increasing body of data indicates that ionizing radiation affects the nervous system and alters its function. Recently, we reported that chemotaxis of during the salt chemotaxis learning (SCL), that is conditioned taste aversion to NaCl, was modulated by carbon ion irradiation, i.e. accelerated decrease in chemotaxis to NaCl during the SCL. However, we had no direct evidence for the interaction of ionizing radiation with the central neuronal tissue (nerve ring) in . Microbeam irradiation is useful to analyze direct radiation effects at a cellular or tissue level. Thus, we applied the microbeam irradiation of the nerve ring and examined the effect on the SCL.
Yokota, Yuichiro; Funayama, Tomoo; Ikeda, Hiroko; Sakashita, Tetsuya; Suzuki, Michiyo; Kobayashi, Yasuhiko
JAEA-Review 2014-050, JAEA Takasaki Annual Report 2013, P. 75, 2015/03
We investigated the bystander effect induced by -rays or carbon ions and analyzed the role of nitric oxide (NO) in the effect. Normal human fibroblasts were used. Cells inoculated on a porous membrane were irradiated with varying doses of -rays or carbon ions. Irradiated cells were then non-contact co-cultured with non-irradiated cells for 24 h. After co-culture, the survival rates of non-irradiated bystander cells co-cultured with irradiated cells decreased with increasing dose and bottomed out at 0.5 Gy or higher doses. This indicates that the bystander effect is dependent on irradiation dose but independent of radiation quality. Next, a specific NO scavenger c-PTIO was added to the culture medium during irradiation and co-culture. This treatment prevented the reduction in survival rates of bystander cells, clearly indicating that NO has an important role in the bystander effect.
locus in normal human fibroblasts induced by C-, Ne- and Ar-ion microbeamsSuzuki, Masao*; Funayama, Tomoo; Yokota, Yuichiro; Muto, Yasuko*; Suzuki, Michiyo; Ikeda, Hiroko; Hattori, Yuya; Kobayashi, Yasuhiko
JAEA-Review 2014-050, JAEA Takasaki Annual Report 2013, P. 78, 2015/03
We have been studying the radiation-quality dependent bystander cellular effects, such as cell killing, mutation induction and chromosomal damage, using heavy-ion microbeams with different ion species. This year we focused on the ion-species dependent bystander mutagenic effect on locus in normal human fibroblasts. The confluent culture were irradiated using a 256 (16
16)-cross-stripe method using C, Ne and Ar microbeam. Gene mutation on locus was detected with 6-thioguanine resistant clones. The mutation frequency in cells irradiated with C-ion microbeams was 6 times higher than that of non-irradiated control cells and of the sample treated with specific inhibitor of gap-junction cell-to-cell communication. On the other hand, no enhanced mutation frequencies were observed in cells irradiated with either Ne- or Ar-ion microbeams. There is clear evidence that the bystander mutagenic effect via gap-junction communication depends on radiation quality.
Tomita, Masanori*; Matsumoto, Hideki*; Otsuka, Kensuke*; Funayama, Tomoo; Yokota, Yuichiro; Suzuki, Michiyo; Sakashita, Tetsuya; Kobayashi, Yasuhiko
JAEA-Review 2014-050, JAEA Takasaki Annual Report 2013, P. 77, 2015/03
Radiation-induced bystander responses are defined as responses in cells that have not been directly targeted by radiation but are in the neighborhood of cells that have been directly exposed. In this study, we aim to clarify a role of bystander response to sustain the homeostasis of damaged tissue using heavy-ion microbeams. We established the heavy-ion microbeam irradiation method to a 3D cultured human epidermis. Using this method, a viable cell rate of the 3D cultured human epidermis irradiated with 260 MeV 
Ne-ion microbeams or broadbeams was analyzed by the MTT method.
and simulation of chemotaxis-related information processing in the neural networkSakamoto, Kazuma*; Soh, Zu*; Suzuki, Michiyo; Kurita, Yuichi*; Tsuji, Toshio*
Proceedings of SAI Intelligent Systems Conference 2015 (IntelliSys 2015), p.668 - 673, 2015/00
in consideration of whole-body movementsSoh, Zu*; Suzuki, Michiyo; Kurita, Yuichi*; Tsuji, Toshio*
Proceedings of SAI Intelligent Systems Conference 2015 (IntelliSys 2015), p.651 - 656, 2015/00
Suzuki, Masao*; Autsavapromporn, N.*; Usami, Noriko*; Funayama, Tomoo; Plante, I.*; Yokota, Yuichiro; Muto, Yasuko*; Suzuki, Michiyo; Ikeda, Hiroko; Hattori, Yuya; et al.
Journal of Radiation Research, 55(Suppl.1), P. i54, 2014/03
based on FitzHugh-Nagumo equationsHattori, Yuya; Suzuki, Michiyo; Soh, Zu*; Kobayashi, Yasuhiko; Tsuji, Toshio*
Artificial Life and Robotics, 17(2), p.173 - 179, 2012/12
Sakashita, Tetsuya; Suzuki, Michiyo; Hamada, Nobuyuki*; Shimozawa, Yoko; Fukamoto, Kana*; Yokota, Yuichiro; Sora, Sakura*; Kakizaki, Takehiko*; Wada, Seiichi*; Funayama, Tomoo; et al.
Biological Sciences in Space, 26, p.21 - 25, 2012/10
High linear energy transfer (LET) radiation is important cosmic rays that has neurobiological effects: it is known to induce conditioned taste aversion, and suppress neurogenesis that may underlie cognitive impairment. However, the impact of high-LET radiation on other learning effects remains largely unknown. Here, we focus on kinetics of the radiation response for the salt chemotaxis learning (SCL) behavior in the nameatode, , because the SCL during the learning conditioning was modulated after low-LET -irradiation. Firstly, the SCL ability was examined following high-LET irradiation (
C, 18.3 MeV/u, LET = 113 keV/m), revealing its dose-dependent decrease after high- and low-LET exposure. Next, we demonstrate that the SCL at the early phase of the learning conditioning is greatly affected by high- and low-LET irradiation, and interestingly, the magnitude of these effects by high-LET radiation was smaller than that by low-LET one. Moreover, the analysis of 
mutant showed that the G-protein subunit, GPC-1 is responsible for such early phase response. This study is the first to provide the evidence for the kinetics of changes in SCL after high-LET irradiation of C. 
.
against high-LET radiation exposureSakashita, Tetsuya; Suzuki, Michiyo; Hamada, Nobuyuki*; Shimozawa, Yoko; Fukamoto, Kana*; Yokota, Yuichiro; Sora, Sakura*; Kakizaki, Takehiko*; Wada, Seiichi*; Funayama, Tomoo; et al.
Biological Sciences in Space, 26, p.7 - 11, 2012/07
Here, we investigated the resistance to high-LET radiation exposure for two behaviors of the nematode, , which is known as a model organism for the nervous system. Tested behaviors were locomotion and chemotaxis to NaCl. In addition, egg hatchability was examined as an indicator of high-LET radiation sensitivity. Relative biological effectiveness (RBE) of high-LET radiation (C, 18.3 MeV/u, LET = 113 keV/m) relative to low-LET radiation for hatchability was 4.5, whereas RBEs for locomotion and chemotaxis were 1.4 and 1.1, respectively. This study shows that the behavioral system for locomotion and chemotaxis of is highly resistant to high-LET radiation exposure.
Hattori, Yuya; Suzuki, Michiyo; Soh, Zu*; Kobayashi, Yasuhiko; Tsuji, Toshio*
Neural Computation, 24(3), p.635 - 675, 2012/03
Times Cited Count：6 Percentile：33.04(Computer Science, Artificial Intelligence)Hattori, Yuya; Suzuki, Michiyo; So, Zu*; Kobayashi, Yasuhiko; Tsuji, Toshio*
Proceedings of 17th International Symposium on Artificial Life and Robotics (AROB 2012) (CD-ROM), p.690 - 695, 2012/01
, for radiation biology as a model organismSakashita, Tetsuya; Suzuki, Michiyo
Hoshasen To Sangyo, (131), p.37 - 41, 2011/12
This review describes the current knowledge of the biological effects of ionizing irradiation with a scope of learning behavior. is well known as a model organism for behavior. The recent work reported the radiation effects via specific neurons on learning behavior, and radiation and hydrogen peroxide affect the locomotory rate similarly. These findings are discussed in relation to the evidence obtained with other organisms. may be a good in vivo model system in the field of radiation biology.
Sakashita, Tetsuya; Suzuki, Michiyo
Hoshasen Seibutsu Kenkyu, 46(1), p.30 - 46, 2011/04
The study of the effects of ionizing radiation on the nervous system is important and potential risk on the nuclear plant accidents and space missions. We have studied the effects of learning behavior of . Here, we report the recent findings on this project, and also review the effects of ionizing radiation on the other organisms. Our findings may provide an important key to understand the human risk.
Sakashita, Tetsuya; Suzuki, Michiyo; Ouchi, Noriyuki; Ban, Nobuhiko*
Hoshasen Seibutsu Kenkyu, 45(4), p.379 - 395, 2010/12
Recently, systems radiation biology (SRB) has been studied and developed in Europe and USA. Also, Japanese researchers in radiation biology are interested in this research field, gradually. In this review, four scientists shortly review SRB in each stand points.
