MECHANISM OF HYPOXIC CELL RADIOSENSITIZATION BY HEAT

这项提案的目的首先是定义葡萄糖的重要性 第二，在高温后低氧细胞的代谢；第二，寻找一种 特异性增强抗辐射低氧细胞杀伤的手段 通过热量和辐射。我们最近的细胞培养研究发现 为我们提供了一些重要线索。由于HeLa细胞在葡萄糖和 氧气缺乏会选择性地对热敏感，我们计划研究 定义碳代谢的具体步骤的中间葡萄糖代谢 与热敏化有关的衬底利用率。 将对HeLa细胞进行研究，以确定 糖酵解、糖异生和己糖单磷酸分流途径 使用特定的代谢抑制剂。后续研究将指导 确定一套文化条件，有效地减少 氧增强率(OER)。具体地说，pH和各种因素的影响 将确定葡萄糖代谢的代谢抑制剂。这个 本研究的意义在于两个方面。第一, 确定任何方法和特定条件以减少 低氧细胞的辐射抗性将有助于更好的应用 热疗和放射治疗的结合。第二，或许同样 同样重要的是，这些数据可能会为 确定癌细胞受热损伤的主要部位。

The objective of this proposal is first to define the importance of glucose metabolism in hypoxic cells following hyperthermia; and second, to find a means to specifically enhance killing of the radioresistant hypoxic cells by heat and radiation. Findings from our recent cell culture studies have provided us with some important clues. Since HeLa cells under glucose and oxygen deprivation become selectively sensitive to heat, we plan to study the intermediary glucose metabolism to define the specific steps of carbon substrate utilization that is related to the thermal sensitization. Studies will be carried out with HeLa cells to determine the importance of glycolysis, gluconeogenesis and hexose monophosphate shunt pathway by the use of specific metabolic inhibitors. Subsequent studies will be directed to determine a set of cultural conditions which will effectively reduce oxygen enhancement ratio (OER). Specifically, the effect of pH and various metabolic inhibitors of glucose metabolism will be determined. The significance of the present studies lies in two areas. First, identification of any method and specific conditions to reduce the radioresistance of hypoxic cells will contribute toward better application of combination hyperthermia and radiation therapy. Second, perhaps equally as important, the data might provide an important clue toward identification of the principal site of hyperthermic damage in cancer cells.