CELLULAR STRESS RESPONSE AND RADIOSENSITIVITY

拟议研究计划的总体目标是测试 假设细胞和核成分参与了 各种应激反应将是反应的决定因素(S) 哺乳动物细胞对电离辐射的治疗用途。一个 这一假设的充分条件是应激反应涉及 电离敏感性的一个或多个可测量决定因素 辐射。此外，这些可测量的决定因素可能是 潜在的临床相关预测分析的候选对象 可能在临床放射肿瘤学中的应用。因此，我们正在 提出了一系列研究项目来调查这些关系 特定的应激反应成分和辐射敏感性之间的关系。 这些压力包括热休克和氧化应激。这个 项目专门针对这些压力，但也包括对 细胞周期扰动，已知的影响压力的后果 放射敏感性、辐射敏感性的核决定因素以及 辐射诱导的DNA损伤对转录的影响，首次报道 参与所有的应激反应。提出了五个单独的项目。 作为基本主题的核心，两个项目(数字3和4)将 研究热诱导放射增敏作用。其中一个将强调 氧化应激成分的作用，另一个将研究其作用 热休克蛋白。其中一个项目(编号5)将研究 从细胞周期扰动中恢复的机制。剩下的 项目(编号1和2)将分别研究分子 DNA损伤对转录的影响及其相互关系 核基质介导的DNA组织和 对辐射敏感。

The overall object of the proposed research program is to test the hypothesis that the cellular and nuclear components involved in various stress responses will be determinants of the response(s) of mammalian cells to therapeutic uses of ionizing radiation. A sufficient condition of this hypothesis is that stress responses involve one or more measurable determinants of the sensitivity to ionizing radiation. Further, such measurable determinants could be candidates for potential clinically relevant predictive assays for possible use in clinical Radiation Oncology. Therefore, we are proposing a series of research projects to investigate the relationships between specific stress response components and radiosensitivity. These stresses include both heat shock and oxidative stress. The projects specifically address these stresses, but also include studies of cell-cycle perturbation, a consequence of stress known to affect radiosensitivity, nuclear determinants of radiosensitivity, and the effects of radiation-induced DNA damage on transcription, a first step in all stress responses. Five individual projects are proposed. Central to the basic theme, two projects, (numbers 3 and 4), will study heat-induced radiosensitization. One of these will emphasize the role of oxidative stress components, the other will study the role of heat-shock proteins. One project, (number 5), will study the mechanisms of recovery from cell-cycle perturbation. The remaining projects, (numbers 1 and 2), will study, respectively the molecular consequences of DNA damage on transcription and the relationship between nuclear matrix mediated DNA organization and radiosensitivity.