MUTATION-TRANSFORMATION: NEUTRON DAMAGE AND REPAIR

本申请提出了突变和/或转化损伤的研究， 和修复所造成的裂变谱中子在啮齿动物和人类细胞 线 我们计划研究转化频率的大幅增强 当来自C3 H 10 T1/2小鼠细胞系的细胞暴露于 长剂量的中子 相比之下，细胞杀伤和突变， 这些细胞似乎没有受到任何大程度的影响， 与在1000 ℃时进行的暴露相比， 高剂量率。 将涉及三个具体领域： 1. 辐射输送方式：将特别重视 极低剂量率和剂量分级研究，以进一步描述 增强的转化频率的程度和小的 对突变频率的影响。 2. 细胞水平的中子作用：在早期的研究中，至少对于 我们假设，修复过程如下： 中子辐照可能容易出错。 我们计划研究 这种错误修复可能会导致遗传性的永久性变化， 通过观察细胞对细胞杀伤、突变和 中子辐照的细胞后代中的转化 人口。 我们还计划同时检查 处理的细胞，以确定是否有任何系统性的变化， 染色体水平可能与敏感性或 易变性 3. 分子水平上的中子作用： 中子对DNA的影响 我们计划使用碱性和中性 洗脱技术，以确定单链和双链 断裂和蛋白质与DNA交联的量发生在 各种治疗方案。 这些检查可以让我们 在DNA水平上的损伤类型和损伤修复， 所看到的转变或突变。

This application proposes a study of mutation and/or transformation damage and repair caused by fission spectrum neutrons in rodent and human cells lines. We plan to investigate the large enhancement of transformation frequency observed when cells from the C3H 10T1/2 mouse cell line are exposed to protracted doses of neutrons. In contrast, cell killing and mutation in these cells do not appear to be influenced to any large degree by protracted exposures to neutrons when compared to exposures delivered at high dose rates. Three specific areas will be addressed: 1. Mode of radiation-delivery: Particular importance will be placed on very low dose rate and dose fractionation studies to further delineate the extent of the enhanced transformation frequency and nature of the small effects on mutation frequency. 2. Neutron action at cellular level: In earlier studies, at least for transformation, we have postulated that the repair processes following neutron irradiation may be prone to mistakes. We plan to examine the possibility that this misrepair would lead to heritable permanent changes in cells by looking at the sensitivity to cell killing, mutation, and transformation in the progeny of cells from neutron-irradiated populations. We also plan to examine concurrently the karyotypes of treated cells to determine if there are any systematic changes at the chromosome level that could be correlated to changes in sensitivity or mutability. 3. Neutron action at molecular level: There is little information about the effects of neutrons on DNA. We plan to use alkaline and neutral elution techniques to determine the number of single- and double-strand breaks and the quantity of protein-to-DNA crosslinking occurring under various treatment regimens. These examinations may enable us to correlate the type of damage and repair of damage at the DNA level with the quantity of transformation or mutations seen.