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

[目的]在治疗脑肿瘤的正常脑组织中通过高辐射来保护正常脑组织，在羟基（OH^·）的yield之间的关系和LET的值被定义为使用X射线和碳束进行分类。在补充中，DNA造成的氧化损伤由低或高LET辐射引起，以衡量8-羟基脱氧瓜氨酸（8-OHdG）的水平。8-OHdG级和LET值之间的关系得到了评估，DNA 3-甲基-1-苯基-2-吡嗪-5 - 1（edaravone）的抗氧化效应也得到了评估，如良好。材料和方法：培养介质（MEM）含有DMPO （200 mmol/L），X射线20戈瑞或290 MeV/u碳束，20-100 keV/μm的辐射范围为20-100 keV/μm。按ESR spectrometer分析OH^. was分析。在1.0毫克/毫升的浓度下将鲑鱼精子DNA浓缩成10戈瑞x射线或290 MeV/u碳束，20-80 keV/μm范围内的溶液。DNA解决方案中的8-OHdG水平是用HPLC和电化学检测器（ECD）测量的。Edaravone将DNA解决方案添加到10微米至1毫米的最终浓度中，8-OHdG水平通过每次辐射后的相同方法进行测量。[Results] The yield of OH^· had a negative logarithmic relationship to LET value。碳离子放射性氢氧在20、40、60、80和90 keV/μm中占86、78、73、69和70%的X射线放射性，因此，相对地，表明间接效应在这些放射性辐射范围内仍然很重要。X射线辐射后的8 OHdG水平大于高辐射后的水平，而X射线辐射后的8 OHdG水平则增加了剂量。这也被证明是，Edaravone显著地抑制了8-OHdO的收益，其保护有效性降低为LET值增加。These unique findings provide further understanding on direct and indirect effect of high-LET radiation in the treatment of brain tumors。

【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.