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Effect of hydroxyl radicals in treatment of malignant brain tumors by accelerated charged particles irradiation

Research Project

Project/Area Number 14571298
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Cerebral neurosurgery
Research InstitutionUniversity of Tsukuba

Principal Investigator

TSUBOI Koji  University of Tsukuba, Institute of Clinical Medicine, Department of Neurological Surgery, Assistant Professor, 臨床医学系, 講師 (90188615)

Co-Investigator(Kenkyū-buntansha) TAKANO Shinngo  University of Tsukuba, Institute of Clinical Medicine, Department of Neurological Surgery, Assistant Professor, 臨床医学系, 講師 (50292553)
ANZAI Kazunori  National Institute of Radiological Sciences, REDOX Research Group, Group Leader, グループリーダー (70128643)
ANDO Koichi  National Institute of Radiological Sciences, Heavy Ion Radiobiology Research Group, Group Leader, グループリーダー (00159526)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywordsradiation / high LET / radicals / edaravone / 8-OHdG / direct effect / indirect effect / brain tumor / 重粒子線
Research Abstract

【Purpose】 In order to protect the normal brain tissue in the treatment of brain tumors by high LET radiation, the relationship between the yield of hydroxyl radicals (OH^・) and values of LET was clarified using x-rays and carbon beams with defined LET. In addition, the oxidative damage of DNA caused by low or high LET radiation by measuring the level of 8-hydroxydeoxyguanosine (8-OHdG). Relationship between the 8-OHdG level and the LET value was assessed, and the anti-oxidative effect of 3-methyl-1-phenyl-2-pyrazonline-5-one (edaravone) on DNA was evaluated as well. 【Materials and methods】 Culture media (MEM) containing DMPO (200 mmol/L) was irradiated with 20 Gy of x-rays or 290 MeV/u carbon beams with a LET range of 20-100 keV/μm. The yield of OH^・ was analyzed by ESR spectrometer. Solution containing salmon sperm DNA at a concentration of 1.0 mg/ml was irradiated with 10 Gy of x-rays or 290 MeV/u carbon beams with an LET range of 20-80 keV/μm. The 8-OHdG level in the DNA solution was measured by HPLC with an electrochemical detector (ECD). Edaravone was added to the DNA solution in final concentrations from 10 μM to 1 mM, and 8-OHdG level was measured by the same method after each irradiation. 【Results】 The yield of OH^・ had a negative logarithmic relationship to LET value. The generation of ^・OH by carbon ion radiolysis at LETs of 20, 40, 60, 80 and 90 keV/μm were 86, 78, 73, 69 and 70% of that for x-ray radiolysis, respectively, indicating that indirect effect is still significant in these LET ranges. The level of 8OHdG after x-ray irradiation was greater than that after high LET irradiation, and the yield of 8-OHdG increased dose-dependently after x-rays irradiation. It was also indicated that edaravone significantly suppressed the yield of 8-OHdO and its protection efficiency decreased as LET value increased. These unique findings provide further understanding on direct and indirect effects of high-LET radiation in the treatment of brain tumors.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] Takano S, Tsuboi K, Matsumura A, Nose T: "Anti-vascular endothelial growth factor antibody and nimustine as combined therapy : effects on tumor growth and angiogenesis in human glioblastoma xenografts."Neurooncol. 5(1). 1-7 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tsuboi K, Saijo K, Ishikawa E, Tsurushima H, Takano S, Morishita Y, Ohno T: "Effects of local injection of ex vivo expanded autologous tumor-specific T lymphocytes in cases with recurrent malignant gliomas."Clin Cancer Res. 9. 3294-3302 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Moritake T, Tsuboi K, Anzai K, Ozawa T, Nose T: "Reduction of nitroxides and radioprotective ability in glioblastoma cells."Brain Tumor Pathol. 20(1). 1-5 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Moritake T, Tsuboi K, Anzai K, Ozawa T, Ando K, Nose T: "ESR spin trapping of hydroxyl radicals in aqueous solution irradiated with high-LET carbon-ion beams."Radiat Res. 159(5). 670-675 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nishizawa K, Moritake T, Matsumaru Y, Tsuboi K, Iwai K: "Dose measurement for patients and physicians using a glass dosemeter during endovascular treatment for brain disease."Radiation Protection Dosimetry. 107(4). 247-252 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 坪井康次, 盛武 敬: "膠芽腫細胞における高LET重イオン線の細胞障害性とラジカル反応に関する研究"放医研シンポジウムシリーズ、第1回重粒子線医科学センターシンポジウム「粒子線治療の基盤展開」-その普及化に向けて-曽我文宣編 独立行政法人放射線医学総合研究所. 68-75 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 盛武 敬, 坪井康次, 安西和紀, 伊古田暢夫, 安藤興一, 小澤俊彦, 能勢忠男: "神経膠腫細胞に対する、重粒子線照射によって生じるラジカル反応に関する基礎的研究 Measurement and protection of the oxidative damage induced by heavy-ion irradiation in human glioblastoma cell lines"平成13年度放射線医学総合研究所重粒子線癌治療装置等共同利用研究報告書.千葉:放射線医学総合研究所. 125-126 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 盛武 敬, 坪井康次, 安西和紀, 伊古田暢夫, 安藤興一, 小澤俊彦: "神経膠腫細胞に対する、重粒子線照射によって生じるラジカル反応に関する基礎的研究 Measurement and protection of the oxidative damage induced by heavy-ion irradiation in human glioblastoma cell lines"平成14年度放射線医学総合研究所重粒子線癌治療装置等共同利用研究報告書.千葉:放射線医学総合研究所. 159-161 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takano S, Tsuboi K, Matsumura A, Nose T.: "Anti-vascular endothelial growth factor antibody and nimustine as combined therapy : effects on tumor growth and angiogenesis in human glioblastoma xenografts."Neurooncol. 5(1). 1-7 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tsuboi K, Saijo K, Ishikawa E, Tsurushima H, Takano S, Morishita Y, Ohno T.: "Effects of local injection of ex vivo expanded autologous tumor-specific T lymphocytes in cases with recurrent malignant gliomas."Clin Cancer Res. 9. 3294-3302 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Moritake T, Tsuboi K, Anzai K, Ozawa T, Nose T.: "Reduction of nitroxides and radioprotective ability in glioblastoma cells."Brain Tumor Pathol. 20(1). 1-5 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Moritake T, Tsuboi K, Anzai K, Ozawa T, Ando K, Nose T.: "ESR spin trapping of hydroxyl radicals in aqueous solution irradiated with high-LET carbon-ion beams."Radiat Res. 159(5). 670-675 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nishizawa K, Moritake T, Matsumaru Y, Tsuboi K, Iwai K.: "Dose measurement for patients and physicians using a glass dosemeter during endovascular treatment for brain disease."Radiation Protection Dosimetry. 107(4). 247-252 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tsuboi K, Moritake T.: "Cytotoxicity and free radical reaction of high LET particles on glioblastoma cells."Proceedings of the 1^<st> HIMAC symposium in NIRS (Edited by Soga F)(Published by National Institute of Radiation Sciences)(in Japanese). June. 68-75 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Moritake T, Tsuboi K, Anzai K, Ikota N, Ando K, Ozawa T, Nose T.: "Measurement and protection of the oxidative damage induced by heavy-ion irradiation in human glioblastoma cell lines."2002 Annual report of the research project with heavy ions at NIRS-HIMAC. April. 125-126 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Moritake T, Tsuboi K, Anzai K, Ikota N, Ando K, Ozawa T.: "Measurement and protection of the oxidative damage induced by heavy-ion irradiation in human glioblastoma cell lines."2003 Annual report of the research project with heavy ions at NIRS-HIMAC. April. 159-161 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Moritake T, Tsuboi K: "Reduction of nitroxides and radioprotection ability in glioblastoma cells"Brain Tumor Pathology. 20. 1-5 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Moritake T, Tsuboi K: "ESR spin trapping of hydroxyl radicals in aqueous solution irradiated with high-LET carbon-ion beams"Radiation Research. 159. 670-675 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nishizawa K, Tsuboi K: "Dose measurement for patients and physicians using a glass dosemeter during endovascular treatment for brain disease"Radiation Protection Dosimetry. 107. 247-252 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 盛武 敬, 坪井康次: "神経膠腫細胞に対する重粒子線によって生じるラジカル反応に関する研究"放射線医学総合研究所. (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 盛武 敬: "神経膠腫に対する重粒子線照射によって生じるラジカル反応の基礎的研究"平成13年度.放医研重粒子線共同利用研究報告書. 130-131 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Moritake T: "ESR spin trapping of Hydroxyl Radical in Aqueous Solution Irradiated with high-LET Carbon-ion Beams"Radiation Research. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Moritake T: "Reduction of nitroxide and radio protective ability in glioblastoma cells"Brain Tumor Pathology. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 坪井康次: "膠芽腫細胞における高LET重イオン線の細胞障害性とラジカル反応に関する研究"放射線医学総合研究所. 163 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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