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

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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.