MECHANISMS IN SHOULDERED SURVIVAL CURVES

肩负生存曲线的机制

• 批准号: 3482045
• 负责人: JOHN R WARD
• 金额: $ 16.84万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-01-01 至 1993-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3482045
• 关键词: DNA damage; DNA repair; DNA replication; HeLa cells; cell cycle; cell death; cellular oncology; hamsters; human subject; ionizing radiation; radiation carcinogenesis; radiation dosage; radiation protection; radiation sensitivity; radiobiology

Repair of ionizing radiation induced damage in mammalian cell DNA is crucial to cell survival. Shoulders on mammalian cell radiation survival curves can be explained by invoking saturation of a repair process at higher doses. To probe this hypothesis, assays of damage are required which can be used at low radiation doses (within the shoulder) as well as high radiation doses. Such assays are proposed here which are effective down to 10 rads, these will be used to test for saturation of repair, measuring rates of repair of DNA single strand breaks, "double strand breaks", and base damage as a function of radiation dose. To probe the significance of these three types of lesions in causing cell death or transformation, attempts will be made to inhibit the repair process and test the result of this inhibition on cell survival or transformation. Also procedures which have been shown to affect cell survival will be probed as to their effects on repair. It is hoped that the information gained from these studies of DNA damage and repair at low doses will be useful in (a) determining the cause of mammalian shouldered survival curves and (b) determining the DNA lesions causing cell death and transformation so that, with the knowledge of cell repair capacity, the hazards of low dose radiation can be extrapolated.

修复哺乳动物细胞DNA的电离辐射诱导损伤为 对细胞存活至关重要。 哺乳动物细胞辐射存活 曲线可以通过调用维修过程的饱和来解释 较高剂量。 为了探究这一假设，需要损坏的测定 可以在低辐射剂量（肩膀内）以及 高辐射剂量。 在这里提出了这样的测定 降至10个rad，这些将用于测试修复的饱和， 测量DNA单链断裂的修复速率，“双链 断裂”，基本损害随辐射剂量的作用。探测 这三种类型的病变在引起细胞死亡或 转型，将尝试抑制维修过程，并 测试这种抑制细胞存活或转化的结果。 同样已显示影响细胞存活的程序将是 探测了它们对维修的影响。 希望这些信息 从低剂量的DNA损伤和修复的这些研究中获得的将是 在（a）确定哺乳动物肩部生存曲线的原因中有用 （b）确定导致细胞死亡和转化的DNA病变 因此，借助细胞修复能力，低的危害 可以推断剂量辐射。