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.

电离辐射对哺乳动物细胞DNA损伤的修复 对细胞生存至关重要。肩上的哺乳动物细胞辐射存活 曲线可以通过调用修复过程的饱和度来解释 更高的剂量。为了探索这一假设，需要对损害进行分析。 它可以在低辐射剂量下(在肩膀内)使用，以及 高辐射剂量。在此提出了有效的分析方法。 低至10拉德，这些将被用来测试修复的饱和度， 测量DNA单链断裂的修复率 断裂“，以及作为辐射剂量函数的碱基损伤。 这三种病变在导致细胞死亡或死亡中的意义 转换，将尝试抑制修复过程和 测试这种抑制细胞存活或转化的结果。 此外，已被证明影响细胞存活的程序将是 探讨了它们对修复的影响。希望这些信息 从这些低剂量DNA损伤和修复的研究中获得的 有助于(A)确定哺乳动物肩状生存曲线的原因 以及(B)确定导致细胞死亡和转化的DNA损伤 因此，随着对细胞修复能力的了解，低风险 剂量辐射可以外推。