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。 由于大多数已发表的关于体内肿瘤的低剂量率照射的结果 与急性剂量率分次辐射和耐受性一样有效 在正常组织上，通常发现随着剂量的减少而增加 如果这些发现，可能会有实质性的治疗收益 被明确定义的特定部位的体内肿瘤所证实。那里 也有一些来自细胞的放射生物学重要性的具体线索 低剂量率照射单独或联合应用的培养研究 需要对体内肿瘤系统进行研究以评估 临床应用。 为了实现特定的目标，将在 两个肿瘤系统。它们是肌肉内生长的RIF-L纤维肉瘤 C3H小鼠和9只L脑内生长的胶质肉瘤 老鼠。每个系统都包含最低限度的低氧细胞群，但非常 防辐射。将进行具体研究，以确定：i) 低剂量率照射对低氧细胞肿瘤的影响 组分和大量非周期肿瘤细胞；ii)关键 超分割照射中的每部分剂量；III)热疗 肿瘤和正常组织的增强比作为函数剂量率 温度为41-43摄氏度。分析终点包括：a) 克隆形成试验，b)肿瘤再生长，c)治愈率。正常的 要研究的组织是皮肤和大脑。 这项研究的意义将是双重的：确定 可能提高低剂量率治疗率的生物因素 放射治疗及其在临床设计中的应用 适用超分割放射治疗。

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.