@misc{oai:repo.qst.go.jp:00064539,
 author = {Autsavapromporn, Narongchai and Suzuki, Masao and Funayama, Tomoo and Usami, Noriko and Yokota, Yuichiro and Mutoh, Yasuko and Ikeda, Hiroko and Iizuka, Toshie and Konishi, Teruaki and Oikawa, Masakazu and Matsufuji, Naruhiro and Uchihori, Yukio and Kobayashi, Katsumi and Kobayashi, Yasuhiko and K, Hei Tom and Azzam, Edouard and Murakami, Takeshi and アッサワプロンポーン ナロンチャイ and 鈴木 雅雄 and 宇佐美 徳子 and 小西 輝昭 and 及川 将一 and 松藤 成弘 and 内堀 幸夫 and 小林 克己 and 村上 健},
 month = {Mar},
 note = {Understanding the mechanism(s) that underlay the non-targeted bystander effects of low or high linear energy transfer (LET) radiations has been considered to be critical for radioprotection, radiotherapy and an assessment of health risks associated with space exploration (1-3). Using microbeam/broad-beam irradiation, we investigated the role of gap junction intercellular communication (GJIC) in modulating radiobiological effects induced in confluent normal human skin fibroblast cultures, which were obtained from Riken Bio Resource in Japan (Cell name: NB1RGB, Cell No.RCB0222), exposed to low doses/fluence of radiations that vary in their quality (i.e. LET from ~6 to 1260 keV/µm). Under condition by which only 0.04% of cells in the population was targeted with monochromatic 5.35 keV X rays (LET ~6 keV/µm), 3.4 MeV protons (LET ~12 keV/µm), 18.3 MeV/u carbon ions (LET ~103 keV/µm), 13.0MeV/u neon ions (LET ~380 keV/µm), or 11.5 MeV/u argon ions (LET ~1260 keV/µm) in the presence or the absence of inhibiting of GJIC. 
     Our results show that carbon ions were more effective than X rays, protons, neon ions and argon ions at inducing cell killing using a colony formation assay. However, inhibiting of GJIC promotes an increase in survival only following exposure to carbon ions. Although the incidence of micronucleus formation induced by X rays shows no different irrespective of irradiation with or/without a gap junction inhibitor, the frequency of micronucleus induced by carbon ions, neon ions and argon ions were significantly higher in the absence of inhibitor than in its presence.  In mutation induction, which was detected in the hypoxanthine-guanine phosphoribosyltransferase (hprt) locus to measure 6-thioguanine resistant clones, there was no different mutation frequency induced by X rays and argon ions in the presence or absence of GJIC inhibitor.  In contrast, reduction of the mutation frequency was observed in cells treated with the GJIC inhibitor exposure to protons, carbon ions and neon ions. Accordingly, this suggests that the LET-dependent track structure of the different ionizing radiations in the biological effect is reflected in biological consequences of cell killing, DNA damage and mutation. Also, GJIC significantly promotes the propagation of stressful bystander effects in high-LET-irradiated cell cultures.
      In conclusion, our data highlight the importance role of radiation quality such as ion species and LET in bystander effects. They are triggered under conditions wherein all cells or a small fraction of cells in the population is irradiated. Characterizing the nature of the communicated molecules between the irradiated and bystander cells would have translational implications in radioprotection and radiotherapy.
Acknowledgements
      This work was supported by International Open Laboratory in National Institute of Radiological Sciences and Japan Society for the Promotion of Science to NA and in part by grants (18310042) from the Ministry of Education, Culture, Sports, Science and Technology in Japan, and the Quantum Beam Technology Program from Japan Science and Technology Agency to MS.
\nReferences
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2.M. Suzuki and C. Tsuruoka. Heavy charged particles produce a bystander effect via cell-cell junctions. Biol. Sci. Space. 18, 241-246 (2004).
3.N. Autsavapromporn, S.M. de Toledo, M. Buonanno, J.-P. Jay-Gerin, A.L. Harris and E. Azzam. Intercellular communication amplifies stressful effects in high-charge, high-energy (HZE) particle-irradiated human cells. J. Radiat. Res. (Tokyo). 52, 408-414 (2011)., 10th International Workshop  Microbeam Probes of Cellular Radiation Response　および Microbeam Training Course},
 title = {Intercellular Communication in the Propagation of Bystander Effect in Human Fibroblasts Induced by Microbeams: The Impact of Radiation Quality},
 year = {2012}
}