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

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【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.