MUTATION-TRANSFORMATION: NEUTRON DAMAGE AND REPAIR

突变转化：中子损伤与修复

• 批准号: 3171721
• 负责人: E HUBERMAN
• 金额: $ 17.66万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-02-01 至 1986-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3171721
• 关键词: DNA repair; X ray; gamma radiation; gene mutation; ionizing radiation; linear energy transfer; mutagens; neutron radiation; radiation carcinogenesis; radiation dosage; radiation related neoplasm /cancer; radiation sensitivity; radiobiology; relative biological effectiveness; tissue /cell culture

Exposure to ionizing radiation is mutagenic as demonstrated in plants, microorganisms, and mammalian cells. Little is known, however, about the processes underlying radiation-induced mutations in mammalian cells, and how the mutagenic process is influenced by the mode of radiation delivery and/or repair processes. Using rodent and human cells, the main objectives of the proposed research are to determine, (1) the dose dependencies for mutation induction by fission-spectrum neutrons from the JANUS reactor, compared to X- or Gamma-rays, and to estimate the relative biological effectiveness (RBE) for this end point; (2) the effect on mutation induction of fractionation and protraction of the radiation dose, for high and low LET radiations (JANUS neutrons, and X or gamma rays, respectively), and whether the mode of delivery indicates a role of repair mechanisms; (3) the effects of different modes of delivery of fission neutrons on the incidence of neoplastic transformation, for comparison with mutation induction to see whether these two end points are mechnistically related; and (4) the interactions of high and low LET radiations in induction of mutation and neoplastic transformation, in order to obtain further insights about the possible mechanisms of their biological actions. The knowledge acquired through this project is also relevant to the understanding of hazards from high LET radiations and to the application of high LET radiations in tumor therapy.

暴露于电离辐射是诱变性的，如在植物中所证明的， 微生物和哺乳动物细胞。 然而，人们对它知之甚少。 哺乳动物细胞辐射诱发突变的基本过程， 诱变过程如何受到辐射传递方式的影响 和/或修复过程。 使用啮齿动物和人类细胞，主要目标是 建议的研究是确定，（1）剂量依赖性 JANUS反应堆的裂变谱中子诱发突变， 与X射线或伽马射线相比， （2）对突变的影响 诱导放射剂量的分割和延长， 和低LET辐射（分别为JANUS中子和X或伽马射线）， 以及交付方式是否表明修复机制的作用;（3） 裂变中子的不同输送方式对 肿瘤转化的发生率，与突变进行比较 归纳以确定这两个终点是否在机理上相关; （4）高、低LET辐射在诱导 突变和肿瘤转化，以获得进一步的见解 关于它们生物学行为的可能机制。 知识 通过这个项目获得的也与理解有关， 高LET辐射的危害和高LET的应用 放射治疗肿瘤