Research of relationship between carbon ion beam resistance and heterochromatin formation in cancer cells

• Project/Area Number: 25861141
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Radiation science
• Research Institution: National Institute of Radiological Sciences
• Principal Investigator: Sato Katsutoshi 国立研究開発法人放射線医学総合研究所, 重粒子医科学センター, 研究員 (20589650)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 粒子線治療 / 炭素イオン線抵抗性 / 炭素イオン線治療 / 放射線抵抗性がん細胞 / ヘテロクロマチン

Outline of Final Research Achievements

Radioresistant cancer cell line X60 and C30 was originally established by means of repeated exposure the mouse squamous cell carcinoma cell line NR-S1 to X-ray and carbon ion beam (C-ion) irradiation, respectively. The results showed that the X60 cells acquired the resistance to both X-ray and C-ion irradiation. On the other hand, the X-ray and C-ion sensitivity of C30 cells was approximately same as that of NR-S1 cells. Moreover, it is shown that the X-ray and C-ion resistance was strongly correlated with the heterchromatin domain number, and the Rad51 focus formation was significantly promoted in X-ray and C-ion resistant X60 cells compared with that in NR-S1 and C30 cells. Our results suggested that homologous recombination repair in heterochromatin region is associated with the X-ray and C-ion resistance in cancer cells.

Research Products

• [Journal Article] A laser-plasma-produced soft X-ray laser at 89 eV generates DNA double-strand breaks in human cancer cells. (2015)
  • Author(s): Katsutoshi Sato, Masaharu Nishikino, Tetsuya Kawachi, Takashi Shimokaw, Takashi Imai, Teruki Teshima, Hiroaki Nishimura, Masaki Kando
  • Journal Title: Journal of Radiation Research Volume: 56 Issue: 4 Pages: 633-638
  • DOI: 10.1093/jrr/rrv015
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Heterochromatin domain number correlates with X-ray and carbon-ion radiation resistance in cancer cells (2014)
  • Author(s): Sato K, Imai T, Okayasu R, Shimokawa T.
  • Journal Title: Radiat. Res. Volume: 182 Issue: 4 Pages: 408-419
  • DOI: 10.1667/rr13492.1
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 放射線治療後の再増殖腫瘍モデルの樹立とこれらの性質変化の解析 (2014)
  • Author(s): 佐藤 克俊, 今井 高志, 下川 卓志
  • Organizer: 日本放射線影響学会第57回大会
  • Place of Presentation: かごしま県民交流センター(鹿児島県・鹿児島市）
  • Year and Date: 2014-10-01 – 2014-10-03
• [Presentation] Repeated carbon ion beam irradiations confer the carbon ion beam resistance but not X-ray resistance in cancer cells (2014)
  • Author(s): Katsutoshi Sato, Takashi Imai, Takashi Shimokawa
  • Organizer: The 73rd Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: パシフィコ横浜（神奈川県・横浜市）
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] Impact of grafted tumor types and host mouse strains on metastasis repression by the C-ion and iDCs combination therapy (2014)
  • Author(s): Ma Liqiu, Katsutoshi Sato, Takashi Imai, Takashi Shimokawa
  • Organizer: The 73rd Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: パシフィコ横浜（神奈川県・横浜市）
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] ハイスループット放射線防護剤スクリーニング法の高度化 (2014)
  • Author(s): 坂本 慶充, 関根 絵美子, 馬 立秋, 佐藤 克俊, 藤崎 真吾, 中西 郁夫, 下川 卓志
  • Organizer: フリーラジカルサマースクール in 館山 2014
  • Place of Presentation: 筑波大学館山研修所（千葉県・館山市）
  • Year and Date: 2014-08-07 – 2014-08-09
• [Presentation] 放射線治療のための併用療法・薬剤の開発 (2014)
  • Author(s): 下川 卓志, 関根 絵美子, 中西 郁夫, 佐藤 克俊
  • Organizer: Biotech2014
  • Place of Presentation: 東京ビッグサイト（東京都・江東区）
  • Year and Date: 2014-05-14 – 2014-05-16
• [Presentation] Characterization of X-ray and carbon ion beam resistant cancer cells for effective control of radioresistant tumor. (2014)
  • Author(s): Katsutoshi Satoh, Takashi Imai, Tyuichi Okayasu, Takashi Shimokawa.
  • Organizer: The 2nd International Symposium of Training Plans for Oncology Professionals
  • Place of Presentation: Osaka, Japan
  • Invited
• [Presentation] Establishment and characterization of novel carbon-ion beam resistance cells (2013)
  • Author(s): Katsutoshi Sato, Daisuke Irie, Miyako Nakamura, Etsuko Nakamura, Hiroyuki Moritake, Takashi Imai, Takashi Shimokawa
  • Organizer: Heavy Ion in Therapy and Space Radiation Symposium 2013 (HITSRS2013)
  • Place of Presentation: Chiba, Japan
• [Presentation] Elucidating the Mechanisms Behind Late Lung Injury after Carbon Ion Beam Irradiation (2013)
  • Author(s): Takashi Shimokawa, Hidetoshi Fujita, Katsutoshi Sato, Miyako Nakawatari, Tomoko Fujita, Hiroyuki Moritake, Ken Ando, Daisuke Irie, Takashi Imai
  • Organizer: Heavy Ion in Therapy and Space Radiation Symposium 2013 (HITSRS2013)
  • Place of Presentation: Chiba, Japan
• [Presentation] Heterochromatin focus number correlates with X-ray and carbon ion beam resistance in cancer cells (2013)
  • Author(s): Katsutoshi Sato, Takashi Imai, Takashi Shimokawa
  • Organizer: The 72nd Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Yokohama, Japan
• [Presentation] Analysis of underlying mechanisms for combination therapy of carbon-ion irradiation and dendritic cell immunotherapy (2013)
  • Author(s): Takashi Shimokawa, Hidetoshi Fujita, Alkihiro Hosoi, Katsutoshi Sato, Kazuhiro Kakimi, Takashi Imai
  • Organizer: The 72nd Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Yokohama, Japan
• [Presentation] Molecular analysis of the different responses of cancer cell to radiation (2013)
  • Author(s): Takashi Imai, Mayumi Fujita, Katsutoshi Sato, Takashi Shimokawa
  • Organizer: The 72nd Annual Meeting of the Japanese Cancer Association.
  • Place of Presentation: Yokohama, Japan
• [Presentation] 放射線治療モデルによる再増殖腫瘍の樹立とその性質の解析 (2013)
  • Author(s): 佐藤 克俊、 入江 大介、今井 高志、 下川 卓志
  • Organizer: 日本放射線影響学会第56回大会
  • Place of Presentation: 青森市
• [Presentation] 炭素イオン線による肺線維化マウスモデルにおけるLETの影響 (2013)
  • Author(s): 下川 卓志、佐藤 克俊、入江 大介、馬 立秋、森竹 浩之、大塚 裕美、菅 和美、中里 真弓、今井 高志
  • Organizer: 日本放射線影響学会第56回大会
  • Place of Presentation: 青森市