| Project/Area Number |
14571298
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | University of Tsukuba |
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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)
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| 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)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| 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)
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| Keywords | radiation / high LET / radicals / edaravone / 8-OHdG / direct effect / indirect effect / brain tumor / 重粒子線 |
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| 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.
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