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Predictive assay of normal tissue damage by irradiation by damage repair process and its clinical application

损伤修复过程对正常组织辐照损伤的预测分析及其临床应用

基本信息

批准号：
16591188
负责人：
KAWATA Tetsuya
金额：
$ 2.3万
依托单位：
Chiba University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

项目摘要

The role of radiotherapy is increasing in cancer therapy, because this treatment modality has many merits in maintaining the normal function and configuration of the organs. The current radiotherapy methods depend on historical experiences and almost similar methods are applied to the patients. However, the radiosensitivity of the patients is expected to be different from the patient to patient. It gives large benefits to patients if their radiosensitivity is predicted before radiotherapy, because the tolerant doses to the normal tissues could be expected and severe damage to them could be avoided It is necessary to clarify the repair of the normal tissue to establish the predictive assay of the normal tissues. The ATM gene is the important gene to react to radiation damage at first. The effect of this gene is inhibited by caffeine. The purpose of this study is to determine the repair suppressive effect of caffeine on the different kinds of cells with impaired ATM gene. The repair suppressive effect of caffeine is determined with FISH as chromosome aberrations. If misrepair can easily detected with FISH, it will be a possible predictive assay method of the normal tissues. In 2004, relationship between cell survival and chromosome aberration after irradiation was determined for both of normal fibroblasts and fibroblasts with abnormal ATM genes. Fibroblasts with abnormal ATM genes had much more chromosome aberration after irradiation, compared with cell survival. This phenomenon suggested that there were many misrepairs in fibroblasts with abnormal ATM genes. In 2005, effect of caffeine on repair after irradiation was determined. Mice with abnormal ATM genes were given whole body irradiation and d survival was determined. However, there was no significant difference between normal mice and mice with abnormal ATM genes. At moment, predictive assay of normal tissues for irradiation with caffeine is not available.

放射治疗在癌症治疗中的作用越来越大，因为这种治疗方式在维持器官的正常功能和结构方面具有许多优点。目前的放射治疗方法依赖于历史经验，并且几乎相似的方法被应用于患者。然而，预期患者的放射敏感性因患者而异。在放射治疗前预测患者的放射敏感性，可以预测正常组织的耐受剂量，避免对正常组织的严重损伤，对患者有很大的益处。ATM基因是辐射损伤反应的重要基因。这种基因的作用被咖啡因抑制。本研究旨在探讨咖啡因对ATM基因受损的不同类型细胞的修复抑制作用。用染色体畸变的荧光原位杂交法测定咖啡因的修复抑制作用。如果FISH技术能很容易地检测出肿瘤的修复异常，那么它将成为一种可能的正常组织的预测性检测方法。2004年，对正常成纤维细胞和ATM基因异常的成纤维细胞，确定了辐射后细胞存活与染色体畸变之间的关系。ATM基因异常的成纤维细胞受照后染色体畸变率明显高于细胞存活率。这一现象提示ATM基因异常的成纤维细胞存在较多的错修复。2005年，咖啡因对辐射后修复的影响被确定。对ATM基因异常的小鼠进行全身照射，并测定d生存率。而正常小鼠与ATM基因异常小鼠之间无明显差异。目前，正常组织对咖啡因照射的预测分析尚不可用。