Enhancement of bystander effects by the inhibition of resistant factors

• Project/Area Number: 19790870
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Radiation science
• Research Institution: Kyoto University
• Principal Investigator: KASHINO Genro Kyoto University, 原子炉実験所, 助教 (00437287)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,650,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥450,000); Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2007: ¥1,700,000 (Direct Cost: ¥1,700,000)
• Keywords: バイスタンダー効果 / 細胞死 / DNA二重鎖切断 / 細胞遊走 / 殺細胞効果

Research Abstract

放射線を照射された細胞集団において、バイスタンダー効果による細胞死、増殖抑制などが知られている。照射後の細胞間または細胞内シグナル伝達経路において、バイスタンダー効果による細胞死を抑制するような因子があるのであれば、それを標的とすることでバイスタンダー効果による細胞死を多く引き起こすことができると考えた。SPring-8 放射光施設では、特殊コリメータの利用により、25 ミクロン幅、200 ミクロン間隔でスダレ状照射が可能である。この照射細胞からのシグナルによる非照射細胞での影響を調べた。その結果、バイスタンダー効果によりDNA 二重鎖切断が誘発されていることが53BP1 フォーカス形成の実験から明らかとなった。この時、照射細胞から分泌される何らかの因子が作用していることが示唆された。また、照射細胞から分泌される因子は、周りの細胞の遊走を促し、ターンオーバーを促している可能性が示唆された。このことから、バイスタンダー効果が致死的影響を及ぼすことは細胞集団のターンオーバーと関連性があることが示唆される。

Research Products

• [Journal Article] Induction of DNA double strand breaks and cellular migration through bystander effects in cells irradiated with the slit type microplanar beam of the Spring-8 synchrotron. (2009)
  • Author(s): Kashino G, Kondoh T, Nariyama N, Umetani K, Ohigashi T, Shinohara K, Kurihara A, Fukumoto M, Tanaka H, Masuhashi A, Suzuki M, Liu Y, Kinashi Y, Masunaga S, Watanabe M, Ono K
  • Journal Title: Int. J. Radiat. Oncol. Bio.l Physic. 74(1) Pages: 229-236
  • Peer Reviewed
• [Journal Article] horylated H2AX Foci in Tumor Cells Have No Correlation with Their Radiation Sensitivities. (2009)
  • Author(s): Yoshikawa T, Kashino G, Ono K, Watanabe M
  • Journal Title: J. Radiat. Res. 50(2) Pages: 151-160
  • Peer Reviewed
• [Journal Article] Spectromicroscopic film dosimetry for high-energy microbeam from synchrotron radiation. (2009)
  • Author(s): Nariyama N, Ohigashi T, Umetani K, Shinohara K, Tanaka H, Maruhashi A, Kashino G, Kurihara A, Kondob T, Fukumoto M, Ono K
  • Journal Title: Appl. Radiat. Isot. 67(1) Pages: 155-159
  • Peer Reviewed
• [Journal Article] Impact of accelerator-based boron neutron capture therapy (AB-BNCT) on the treatment of multiple liver tumors and malignant pleural mesothelioma. (2009)
  • Author(s): Suzuki M, Tanaka H, Sakurai Y, Kashino G, Yong L, Masunaga S, Kinashi Y, Mitsumoto T, Yajima S, Tsutsui H, Sato T, Maruhashi A, Ono K
  • Journal Title: Radiother. Oncol. (in press)
  • Peer Reviewed
• [Journal Article] The effect of post-irradiation tumor oxygenation status on recovery from radiation-induced damage in vivo: with reference to that in quiescent cell populations. (2009)
  • Author(s): Masunaga SI, Hirayama R, Uzawa A, Kashino G, Suzuki M, Kinashi Y, Liu Y, Koike S, Ando K, Ono K
  • Journal Title: J. Cancer Res. Clin. Oncol. (in press)
  • NAID: 120001624124
  • Peer Reviewed
• [Journal Article] Evaluation of the potential of hexamethylenetetramine, compared with tirapazamine, as a combined agent with {gamma}-irradiation and cisplatin treatment in vivo. (2009)
  • Author(s): Masunaga S, Tano K, Watanabe M, Kashino G, Suzuki M, Kinashi Y, Ono K, Nakamura J
  • Journal Title: Br. J. Radiol. (in press)
  • Peer Reviewed
• [Journal Article] Usefulness of hexamethylenetetramine in combination with chemotherapy using free and pegylated liposomal doxorubicin in vivo, referring to the effect on quiescent cells. (2009)
  • Author(s): Masunaga S, Kono K, Nakamura J, Tano K, Yoshida H, Watanabe M, Kashino G, Suzuki M, Kinashi Y, Liu Y, Ono K.
  • Journal Title: Oncol. Rep. 21(5) Pages: 1307-1312
  • Peer Reviewed
• [Journal Article] Induction of DNA double strand breaks and cellular migration through bystander effects in cells irradiated with slit-type microplanar beam of SPring-8 synchrotron (2009)
  • Author(s): Kashino G, et.al.
  • Journal Title: International Journal of Radiation Oncology, Biology, Physic 74 Pages: 229-236
  • Peer Reviewed
• [Journal Article] Phosphorylated H2AX foci in tumor cells have no correlation with their radiation sensitivities (2009)
  • Author(s): Yoshikawa T, Kashino G, et.al.
  • Journal Title: Journal of Radiation Research 50 Pages: 151-160
  • NAID: 10025911507
  • Peer Reviewed
• [Journal Article] Different involvement of radical species in irradiated and bystander cells. (2008)
  • Author(s): Harada T, Kashino G, Suzuki K, Matsuda N, Kodama S, Watanabe M
  • Journal Title: Int. J. Radiat. Biol. 84(4) Pages: 809-814
  • Peer Reviewed
• [Journal Article] Radiobiologic significance of response of intratumor quiescent cells in vivo to accelerated carbon ion beams compared with gamma-rays and reactor neutron beams. (2008)
  • Author(s): Masunaga S, Ando K, Uzawa A, Hirayama R, Furusawa Y, Koike S, Sakurai Y, Nagata K, Suzuki M, Kashino G, Kinashi Y, Tanaka H, Maruhashi A, Ono K.
  • Journal Title: Int. J. Radiat. Oncol. Biol. Phys. 70(1) Pages: 221-228
  • NAID: 130007001332
  • Peer Reviewed
• [Journal Article] Different involvement of radical species in irradiated and bystander cells (2008)
  • Author(s): Harada T, Kashino G, et.al.
  • Journal Title: International Journal of Radiation Biology 84 Pages: 809-814
  • Peer Reviewed
• [Presentation] Involvement of the secreted factors and radical species by X-irradiations on the induction of bystander effects (2008)
  • Author(s): Kashino G
  • Organizer: An International Symposium of Kyoto University RRI
  • Place of Presentation: Kumatori, Osaka
  • Year and Date: 2008-12-18
• [Presentation] DMSOによる放射線防護効果の機構解析 (2008)
  • Author(s): 菓子野元郎ら
  • Organizer: 第47回日本医学放射線学会生物部会学術大会
  • Place of Presentation: 高知
  • Year and Date: 2008-06-21
• [Presentation] Bystander effects in microplanar beam irradiated glioma cells (2008)
  • Author(s): Kashino G, et.al.
  • Organizer: New Prospects for Brain Tumor Radiotherapy : Synchrotron Light and Microbeam Radiation Therapy
  • Place of Presentation: Grenoble, France
  • Year and Date: 2008-06-02
• [Presentation] 微小平板ビーム照射されたグリオーマ細胞におけるバイスタンダー効果 (2008)
  • Author(s): 菓子野元郎、近藤威、栗原愛、福本学、篠原邦夫、鈴木実、増永慎一郎、渡邉正己、小野公二
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] 微小平板ビーム療法における殺細胞効果の解析 (2008)
  • Author(s): 菓子野元郎、近藤威、栗原愛、福本学、劉勇、鈴木実、増永慎一郎、木梨友子、小野公二
  • Organizer: 日本放射線腫瘍学会第21回学術大会
  • Place of Presentation: 札幌
• [Presentation] Radiation induced bystander effects in glioma (2008)
  • Author(s): 菓子野元郎、劉勇、鈴木実、木梨友子、増永慎一郎、渡邉正己、小野公二
  • Organizer: 第9回文部科学省特定領域研究「がん」5 領域若手研究者ワークショップ
  • Place of Presentation: 蓼科
• [Presentation] Bystander effects in microplanar beam irradiated glioma cells, New Prospects for Brain Tumor Radiotherapy : Synchrotron Light and Microbeam Radiation Therapy (2008)
  • Author(s): G. Kashino, T. Kondoh, N. Nariyama, T. Ohigashi, K. Umetani, K. Shinohara, A. Kurihara, M. Fukumoto, H. Tanaka, A. Maruhashi, M. Suzuki, Y. Kinashi, S. Masunaga, M. Watanabe, K. Ono,
  • Organizer: SYRAD workshop
  • Place of Presentation: Grenoble
• [Presentation] マイクロビーム照射により培養細胞集団に及ぼされるバイスタンダー効果 (2008)
  • Author(s): 菓子野元郎、鈴木実、木梨友子、増永慎一郎、小野公二、渡邉正己
  • Organizer: 日本組織培養学会第81回大会
• [Presentation] The role of DNA double strand breaks repair in radiation induced bystander responses (2007)
  • Author(s): Genro Kashino, et. al.
  • Organizer: International Congress of Radiation Research
  • Place of Presentation: サンフランシスコ
  • Year and Date: 2007-07-09