Combination treatment with carbon ions and Hsp90 inhibitor 17-AAG

• Project/Area Number: 19890271
• Research Category: Grant-in-Aid for Young Scientists (Start-up)
• Allocation Type: Single-year Grants
• Research Field: Radiation science
• Research Institution: Japan Atomic Energy Agency
• Principal Investigator: NOGUCHI Miho Japan Atomic Energy Agency, 先端基礎研究センター, 研究職 (40455283)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,033,000 (Direct Cost: ¥2,640,000、Indirect Cost: ¥393,000); Fiscal Year 2008: ¥1,703,000 (Direct Cost: ¥1,310,000、Indirect Cost: ¥393,000); Fiscal Year 2007: ¥1,330,000 (Direct Cost: ¥1,330,000)
• Keywords: 粒子線治療 / 炭素線治療 / 17-AAG / 増感 / Hsp90 / 炭素イオン線 / 放射線増感 / 細胞周期 / G2チェックポイント / Herbimycin / DNA二本鎖切断修復

Research Abstract

炭素イオン線照射(以下、炭素線)に化学療法剤であるHsp90阻害剤17-AAGを併用し、炭素線による細胞致死効果の増強を試みた。その結果、前立腺癌細胞で両者の併用により炭素線照射効果が増強され、細胞死が顕著に増加した。この原因として17-AAGによるDNA二本鎖切断(以下、DSB)の修復阻害が考えられたが、炭素線により誘発されたDSBはそれ自体、非常に修復しにくく、17-AAGによる修復阻害の増強は認められなかった。しかし、M期細胞で微小核が増加したことから、17-AAGは細胞分裂の異常を引き起こし、最終的に細胞死を誘導することが示唆された。

Research Products

• [Journal Article] Sergey Druzhinin and Ryuichi Okayasu, Enhanced Radiation Induced Cell Killing by Herbimycin A Pre-treatment (2009)
  • Author(s): Miho Noguchi, Ryoichi Hirayama
  • Journal Title: Radiation Physics and Chemistry (in press)
  • Peer Reviewed
• [Journal Article] The yield, processing, and biological consequences of clustered DNA damage induced by ionizing radiation (2009)
  • Author(s): Naoya shikazono, Miho Noguchi, Kentaro Fujii, Ayumi Urushibara and Akinari Yokoya
  • Journal Title: Journal of Radiation Research 50 Pages: 27-36
  • NAID: 110007042080
  • Peer Reviewed
• [Journal Article] Contributions of Direct and Indirect Actions in Cell Killing by High LET Radiations (2009)
  • Author(s): Ryoichi Hirayama, Atsushi Ito, Masanori Tomita, Masako Izumi, Fumio Yatagai, Miho Noguchi, Yoshitaka Matsumoto, Yuki Kase, Koichi Ando, Ryuichi Okayasu and Yoshiya Furusawa
  • Journal Title: Radiation Research 171 Pages: 212-218
  • Peer Reviewed
• [Journal Article] Enhanced Radiation Induced Cell Killing by Herbimycin A Pre-treatment (2009)
  • Author(s): Miho Noguchi, Ryoichi Hirayama, Sergey Druzhinin, Ryuichi Okayasu
  • Journal Title: Radiation Physics and Chemistry (印刷中)
  • Peer Reviewed
• [Journal Article] The yield, processing, and biological consequences of clustered DNA damage induced by ionizing radiation (2009)
  • Author(s): Naoya shikazono, Miho Noguchi, Kentaro Fujii, Ayumi Urushibara, Akinari Yokoya
  • Journal Title: Journal of Radiation Research 50 Pages: 27-36
  • NAID: 110007042080
  • Peer Reviewed
• [Journal Article] Contributions of Direct and Indirect Actions in Cell Killing by High LET Radiations (2009)
  • Author(s): Ryoichi Hirayama, Atsushi Ito, Masanori Tomita, Masako Izumi, Fumio Yatagai, Miho Noguchi, Yoshitaka Matsumoto, Yuki Kase, Koichi Ando, Ryuichi Okayasu, Yoshiya Furusawa
  • Journal Title: Radiation Research 171 Pages: 212-218
  • Peer Reviewed
• [Journal Article] Radioprotection by DMSO in Nitrogen Saturated Mammalian Cells Exposed to Helium Ion Beams (2009)
  • Author(s): Ryoichi Hirayama, Yoshitaka Matsumoto, Yuki Kase, Miho Nougchi, Koichi Ando, Atsushi Ito, Ryuichi Okayasu, Yoshiya Furusawa
  • Journal Title: Radiation Physics and Chemistry (印刷中)
  • Peer Reviewed
• [Journal Article] Radiobiology for Heavy-ion Radiotherapy (2008)
  • Author(s): Ryuichi Okayasu, Takamitsu Kato, Miho Noguchi, Maki Okada and Emiko Sekine
  • Journal Title: Proceedings of NIRS-MDA Symposium on Clinical Issues for Particle Therapy Pages: 174-180
• [Journal Article] Radiobiology for Heavy-ion Radiotherapy (2008)
  • Author(s): Ryuichi Okayasu, Takamitsu Kato, Miho Noguchi, Maki Okada, Emiko Sekine
  • Journal Title: Proceedings of NIRS-MDA Symposium on Clinical Issues for Particle Therapy Pages: 174-180
• [Journal Article] ゲルダナマイシン誘導体の併用による癌の放射線治療 (2007)
  • Author(s): 岡安 隆一、野口 実穂
  • Journal Title: ISOTOPE NEWS 643 Pages: 2-7
• [Journal Article] 高LET重粒子線によるDNA二重鎖切断損傷とその修復 (2007)
  • Author(s): 岡安 隆一、岡田 真希、岡部 篤史、野口 実穂
  • Journal Title: 癌の臨床 53 Pages: 371-375
• [Journal Article] ゲルダナマイシン誘導体の併用による癌の放射線治療
  • Author(s): 岡安隆一、野口実穂
  • Journal Title: ISOTOPE NEWS 643 Pages: 2-7
• [Presentation] 8-oxoGを含むクラスターDNA損傷誘発突然変異における一本鎖切断の影響 (2008)
  • Author(s): 野口実穂
  • Organizer: 日本放射線影響学会第51回大会
  • Place of Presentation: 北九州市
• [Presentation] Enhanced Radiation Induced Cell Killing by Herbimycin A Pre-treatment (2008)
  • Author(s): Miho Noguchi
  • Organizer: The 2nd Asia-Pacific Symposium on Radiation Chemistry
  • Place of Presentation: 東京
• [Presentation] Mutagenic potential of 8-oxo-7,8-dihydroguanine depends on single strand break location (2008)
  • Author(s): Miho Noguchi,
  • Organizer: 10th International Workshop Radiation Damage to DNA
  • Place of Presentation: 裏磐梯
• [Presentation] Radiobiology for heavy-ion radiotherapy (2008)
  • Author(s): Ryuichi Okayasu, Takamitsu Kato, Miho Noguchi, Maki Okada, Emiko Sekine
  • Organizer: NIRS-MDA Symposium on Clinical Issues for Particle Therapy
  • Place of Presentation: Houston, USA
• [Presentation] Mutagenic potential of 8-oxo-7,8-dihydroguanine depends on single strand break location (2008)
  • Author(s): Miho Noguchi, Ayumi Urushibara, Akinari Yokoya, Peter O'Neill, Naoya Shikazono
  • Organizer: 10th International Workshop Radiation Damage to DNA
  • Place of Presentation: Urabandai, Japan
• [Presentation] Contribution of indirect action of X-irradiation under oxic and hypoxic conditions in different radiosensitivity cells (2008)
  • Author(s): Ryoichi Hirayama, Yoshiya Furusawa, Atsushi Ito, Miho Noguchi, Yoshitaka Matsumoto, Akiko Uzawa, Koichi Ando, Ryuichi Okayasu
  • Organizer: 10th International Workshop Radiation Damage to DNA
  • Place of Presentation: Urabandai, Japan
• [Presentation] NHEJ修復欠損xrs6細胞における放射線作用の細胞致死効果 (2008)
  • Author(s): 平山亮一, 古澤佳也, 伊藤敦, 野口実穂, 松本孔貴, 鵜澤玲子, 安藤興一, 岡安隆一
  • Organizer: 日本放射線影響学会第51回大会
  • Place of Presentation: 北九州市
• [Presentation] 鎖切断と脱塩基部位からなるクラスターDNA損傷の生物効果 (2008)
  • Author(s): 鹿園直哉, 野口実穂, 漆原あゆみ, Peter O'Neill, 横谷明徳
  • Organizer: 日本放射線影響学会第51回大会
  • Place of Presentation: 北九州市
• [Presentation] 大気下ならびに無酸素下でのOHラジカルによる間接作用の細胞致死効果 (2007)
  • Author(s): 平山 亮一、野口 実穂、伊藤 敦、安藤 興一、古澤 佳也、岡安 隆一
  • Organizer: 日本放射線影響学会第50回大会
  • Place of Presentation: 千葉市
  • Year and Date: 2007-11-15
• [Presentation] The mutation frequency of 8-oxo-7, 8-dihydroguanine when single strandbreak is closely present on the saiae or the opposite strand (2007)
  • Author(s): Miho Nogucbi, Ayumi Urushibara, Akinari Yokoya, Naoya Shikazono
  • Organizer: The 7th International Symposium on Advanced Scfence Research
  • Place of Presentation: 茨城県東海村
  • Year and Date: 2007-11-08
• [Presentation] Hsp90阻害剤による放射線増感〜DNA二本鎖切断修復への影響〜 (2007)
  • Author(s): 野口 実穂, 于 冬, 平山 亮一, 窪田 宜夫, 岡安 隆一
  • Organizer: 第46回日本医学放射線学会生物部会
  • Place of Presentation: 茨城県つくば市
  • Year and Date: 2007-07-21
• [Presentation] DNA損傷で観たin vitroとin vivoにおける酸素効果 (2007)
  • Author(s): 平山 亮一, 鵜沢 玲子, 野口 実穂, 松本 孔貴, 渡辺 雅彦, 小池 幸子, 古澤 佳也, 安藤 興一, 岡安 隆一
  • Organizer: 第46回日本医学放射線学会生物部会
  • Place of Presentation: 茨城県つくば市
  • Year and Date: 2007-07-21
• [Presentation] 17-allylamino-17-demethoxygeldanamycin enhances the cytotoxicity of tomor cells irradiated with carbon ions (2007)
  • Author(s): Miho Noguchi, Ryoichi Hirayama, Dong Yu, Koichi Ando, Ryuichi Okayasu
  • Organizer: 13th International Congress of Radiation Research
  • Place of Presentation: サンフランシスコ(米国)
  • Year and Date: 2007-01-10
• [Presentation] 非二本鎖切断型クラスター損傷(8-oxoGと鎖切断)の突然変異誘発 (2007)
  • Author(s): 野口実穂
  • Organizer: 日本放射線影響学会第50回大会
  • Place of Presentation: 千葉市
• [Presentation] The mutation frequency of 8-oxo-7,8-dihydroguanine when single strand break is closely present on the same or the opposite strand (2007)
  • Author(s): Miho Noguchi,
  • Organizer: The 7th International Symposium on Advanced Science Research
  • Place of Presentation: 茨城県つくば市
• [Book] 診療放射線技師ポケットレビュー帳 (2008)
  • Author(s): 福士政弘(編集)、野口実穂、寺下貴美, ほか
  • Publisher: メジカルビュー社