Investigation of molecular mechanism of radiosensitivity of the tumor cell and its clinical application

肿瘤细胞放射敏感性分子机制研究及其临床应用

• 批准号: 08671043
• 负责人: SAKATA Koh-ichi
• 金额: $ 1.6万
• 依托单位: SAPPORO MEDICAL UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08671043/
• 关键词: DNA-PK; radiosensitivity; multicellular spheroids; potentially lethal damage

1.We measured the activity of DNA-PK (DNA-dependent protein kinase) of two established cell lines that have the different radiosensitivity. One of them was HK-1 (malignant lymphoma) and the other was Suzuki(thyroid cancer). Suzuki is more radiosensitive than HK-1. However, there was no significant difference of the activity of DNA-PK between them.2.We made samll multicellular spheroids 100 mum in diameter with human osteosarcoma cell line (MG-63) to examine whether there was the difference of the activity of DNA-PK between monolayr and spheroid culture. MG-63 cells in spheroid culture become more radioresistant than monolayr culture. We used MG-63 cells of log phase and confluent phase of growth in monolayr culture as a control. However, there was no significant difference of the activity of DNA-PK in monolayr culture and spheroid culture.3.There are two processes of repair of potentially lethal damage following X irradiaiton ; a rapid repair process, which is completed in about 1 hour, is interrupted by hypertonic saline treatment, and a slower process, which requires several hours to be completed, is facilitated by the application of condititioned medium. As a medhanism of inhibition of a rapid repair process by hypertonic saline treatment, there was the possibility that hypertonic saline treatment might block the repair of DNA double strand break by inhibiting the activity of DNA-PK.Then, we used two types of malignant melanoma cell lines to check such possibility. G-361 cells (D_0=145cGy, Dq=249cGy) are more radioresistant and have the higher ability of a rapid repair process of PLD than P39 (D_0=74cGy, Dq=85cGy). However, in both cel lines, there was no significant difference of the activity of DNA-PK between groups with hypertonic saline treatment and those without treatment.

1.测定了两种辐射敏感性不同的细胞系的DNA-PK(DNA依赖蛋白激酶)活性。其中一例为HK-1(恶性淋巴瘤)，另一例为铃木(甲状腺癌)。铃木比HK-1对辐射更敏感。2.以人骨肉瘤细胞系MG-63为材料，制作直径为100微米的小片多细胞球体，观察单层和球体培养的DNA-PK活性是否存在差异。球形培养的MG-63细胞比单层培养的MG-63细胞具有更强的辐射抗性。以单层培养对数生长期和融合生长期MG-63细胞为对照。然而，DNA-PK活性在单层培养和球形培养中没有显著差异。3.X射线照射后潜在致命性损伤的修复有两个过程：一个快速修复过程约在1小时内完成，高渗盐水处理中断一个较慢的修复过程，需要几个小时才能完成。作为高渗盐水抑制快速修复过程的一种机制，高渗盐水处理有可能通过抑制DNA-PKs的活性来阻断DNA双链断裂的修复。G-361细胞(D_0=145cGY，DQ=249cGY)比P39(D_0=74cGY，DQ=85cGY)具有更强的抗辐射能力和更强的快速修复PLD的能力。高渗盐水处理组和未处理组DNA-PK活性差异无统计学意义。