@misc{oai:repo.qst.go.jp:00071151, author = {Autsavapromporn, Narongchai and Suzuki, Masao and Hua, Liu Cui 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 劉 翠華 and 村上 健}, month = {Jun}, note = {Aim: Radiation-induced bystander effect (RIBE) has important implication in radiotherapy (1-3), but the bystander signal between irradiated cancer cells and bystander cells are still not well known. Our experiments were aimed at evaluating this concept. Method: Human glioma (T98G) cells were irradiated with a single doses of 6 Gy or doses divided into 3 fractions given at consecutive days (3 x 2 Gy) of carbon ions and then co-cultured with fibroblasts (NB1RGB), in the presence or absence of gap-junction inhibitor AGA for 4 h using the layered tissue culture system which allows co-culturing the irradiated-T98G cells growing in wells with bystander NB1RGB cells growing in inserts (2), and medium transfer strategy (3). Bystander NB1RGB cells were then harvested and assayed for clonogenic survival and micronucleus formation (MN). Results: Relative to control, both single dose irradiation and fractionation of the dose into three fractions show the bystander NB1RGB cells exhibited reduced cloning efficiency and consistence with increased of MN formation. In contrast, treatment with AGA shows a significant increase of survival and decrease of MN formation in bystander cells. These indicated that gap-junction intercellular communication in the propagation of RIBE. Interestingly, the condition medium harvested from irradiated T98 cells receiving fractionated irradiation presented lower cloning efficiency and a higher MN formation than a single-dose irradiation. These results suggested that fractionated irradiation removed the effect of dose sparing that is observed after conventional fractionated regime. Conclusions: Our results provide the evidence that RIBE in both single dose irradiation and fractionated irradiation, which were observed in bystander fibroblasts indicating that irradiated cancer cells can induce damage in normal cells. Characterizing the nature of the communicated molecules would have translational implications in radiotherapy and radioprotection. References 1. Autsavapromporn N., Suzuki M., Funayama T., Usami U., Plante I., Yokota Y., Mutou Y., Ikeda H., Uchihori Y., Kobayashi K., Kobayashi Y., Hei T.K., Azzam E.I. and Murakami T. Gap Junction Communication in the Propagation of Bystander Effect in Human Fibroblasts induced by Microbeams: The Impact of Radiation Quality, Radiation Research (Submitted) 2. Wakatsuki M., Magpayo N., Kawamura H. and Held K.D. Differential Bystander Signaling Between Radioresistant Chondrosarcoma Cells and Fibroblasts After X-ray, Proton, Iron Ion and Carbon Ion Exposures. International Journal of Radiation Oncology, Biology, Physics (2012), 84: e103-e108. 3. Mothersill C. and Seymour C.B. Bystander and Delayed Effects after Fractionated Radiation Exposure. Radiation Research (2002), 158: 626-633., 52nd Annual Conference of the Particle Therapy Co-Operative Group}, title = {Intercellular Communication Between Carbon-Irradiated Cancer Cells and Non-Irradiated Bystander Fibroblasts: The Impact of Fractionated Irradiation}, year = {2013} }