权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Radiobiological factors determining the radiosensitivity of radioresistant cancer cells

决定放射抗性癌细胞放射敏感性的放射生物学因素

基本信息

批准号：
06670906
负责人：
YAMADA Ichiro
金额：
$ 1.34万
依托单位：
Tokyo Medical and Dental University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06670906/
关键词：
Radioresistance Cancer Cells Radiobiology Melanoma Cells Radiosensitivity PLD Repair Cell Kinetics

项目摘要

In an attempt to elucidate the mechanism of radioresistance in melanoma cells, we demonstrated the following facts in the experimental system using human and murine melanoma cells : (1) the radiation dose-survival curve in melanoma cells had a larger shoulder portion in the low dose region, showing a marked radioresistance to doses commonly used in the conventional fractionated radiotherapy ; (2) melanoma cells showed a prominent repair of potentially lethal damage (PLD) after irradiation ; (3) melanoma cells had a relatively high fraction of S-phase cells which were more radioresistant than other phase cells in the cell cycle ; and, (4) pretreatment of melanoma cells with L-dopa significantly reduced the capacity for sublethal radiation damage in melanoma cells.On the basis of these results, we have studied the cell kinetics, melanin production, GSH metabolism, and DNA repair, so as to further elucidate the mechanism of radioresistance of melanoma cells. All of melanin-producing melanoma cell lines showede a larger shoulder portion in the low dose region and a larger repair of PLD in various conditioned examined. The synchronized culture method demonstrated the change of radiosensitivity during the cell cycle and the survival curves of cells in each phase of the cell cycle. GSH levels and GSH-related enzymes activity were examined, suggesting the relationship between the GSH metabolism and radiosensitivity. Further, unscheduled DNA synthesis (UDS) after irradiation were also examined, so as to elucidate the relationship between the DNA repair and radiosensitivity.

为了阐明黑色素瘤细胞的放射抵抗机制，我们在使用人和小鼠黑色素瘤细胞的实验系统中证明了以下事实：（1）黑色素瘤细胞的放射剂量-生存曲线在低剂量区域有较大的肩部，显示出对常规分割放射治疗中常用剂量的明显放射抵抗； (2) 黑色素瘤细胞在照射后表现出显着的潜在致命损伤（PLD）修复； (3)黑色素瘤细胞中S期细胞比例相对较高，其比细胞周期中其他期细胞更具有抗辐射能力； (4)左旋多巴预处理黑色素瘤细胞，显着降低黑色素瘤细胞亚致死辐射损伤的能力。在此基础上，我们对细胞动力学、黑色素生成、谷胱甘肽代谢和DNA修复等进行了研究，以进一步阐明黑色素瘤细胞的放射抵抗机制。所有产生黑色素的黑色素瘤细胞系在低剂量区域均显示出较大的肩部，并且在各种条件检查中显示出较大的 PLD 修复。同步培养方法展示了细胞周期过程中放射敏感性的变化以及细胞周期各时相细胞的存活曲线。检查 GSH 水平和 GSH 相关酶活性，提示 GSH 代谢与放射敏感性之间的关系。此外，还检查了照射后的非计划DNA合成（UDS），以阐明DNA修复与放射敏感性之间的关系。