LOW DOSE RATE RADIOTHERAPY AND HYPERTHERMIA

该提案的总体目标是确定放射生物学因素 与超分割放射治疗的设计有关。 由于大多数发表的结果低剂量率照射在体内肿瘤 与急性剂量率、分次辐射和耐受性一样有效 通常发现正常组织上的剂量随着剂量的减少而增加 率，实质性的治疗收益可能是预期的，如果这些发现 在特定部位的明确体内肿瘤中得到证实。 那里 也有一些来自细胞的放射生物学重要性的具体线索 低剂量率辐射单独或与 需要用体内肿瘤系统进行研究以评估 临床应用 为了实现具体目标，将进行实验， 两个肿瘤系统 它们是生长在肌内的RIF-1纤维肉瘤 在C3 H小鼠和9 L胶质肉瘤生长在脑内Fischer 大鼠 每个系统都含有最少的缺氧细胞群，但非常 抗辐射的 具体的研究将直接确定：i） 低剂量率照射对乏氧细胞肿瘤影响 部分和大的非循环肿瘤细胞群体; ii）关键的 超分割照射中的每部分剂量; iii）热 肿瘤和正常组织的增强比作为剂量率的函数， 温度为41 - 43 ℃。 分析终点将包括：a） 克隆形成测定，B）肿瘤的再生长，c）治愈率。 正常 待研究的组织是皮肤和大脑。 这项研究的意义有两个方面： 可能提高低剂量率治疗率的生物学因素 放射治疗和应用的研究结果，以设计临床 超分割放射治疗。

The overall aim of the proposal is to identify radiobiological factors relevant to the design of hyperfractionated radiotherapy. Since most published results of low dose rate irradiation on in vivo tumors are as effective as acute dose rate fractionated radiations and tolerance on the normal tissues are generally found to be increased with reduced dose rate, substantial therapeutic gains might be anticipated, if these findings are confirmed with well-defined in vivo tumors of specific sites. There are also some specific clues of radibiological importance derived from cell culture studies of low dose rate irradiation alone or in combination with heat that requires a study with in vivo tumor system for assessment of clinical application. In order to achieve the specific aims, experiments will be carried out with two tumor systems. They are the RIF-l fibrosarcoma growing intramuscularly in C3H mice and the 9 L gliosarcoma growing intracerebrally in Fischer rats. Each system contain minimal hypoxic cell populations, but are very radioresistant. Specific studies will be directed to determine: i) the influence of low dose rate irradiation on tumors with minimal hypoxic cell fraction and with large noncycling tumor cell population; ii) the critical dose per fraction in hyperfractionated irradiation; iii) thermal enhancement ratio of tumors and normal tissues as a function dose rates at temperatures of 41 -43 C. The endpoints of analysis will include: a) clonogenic assays, b) regrowth of tumors, c) cure rates. The normal tissues to be studied are skin and brain. The significance of the study would be two-fold: identification of biological factors that might improve therapeutic ratio of low dose rate radiotherapy and application of the findings to the design of clinically applicable hyperfractionated radiotherapy.