MUTATION-TRANSFORMATION: NEUTRON DAMAGE AND REPAIR

本申请提出了突变和/或转化损伤的研究 以及由裂变能谱中子引起的啮齿动物和人类细胞的修复 台词。 我们计划研究转化频率的大幅提高 C3H10T1/2小鼠细胞暴露于 长期剂量的中子。相比之下，细胞的杀伤和突变 这些细胞似乎没有受到任何很大程度的影响 长期暴露于中子，而不是暴露在 高剂量率。将涉及三个具体领域： 1.辐射传输方式：将特别重视 极低剂量率和剂量分级研究，以进一步描绘 增强程度的转变频率和性质都不大 对突变频率的影响。 2.在细胞水平上的中子作用：在早期的研究中，至少 转换，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 这种错误修复将导致可遗传的永久性变化的可能性 通过观察细胞对细胞杀伤、突变和 中子照射后细胞子代的转化 人口。我们还计划同时检查人类的核型。 处理过的细胞，以确定在 染色体水平可能与敏感度或 易变性。 3.分子水平上的中子作用：关于以下方面的信息很少 中子对DNA的影响。我们计划使用碱性和中性 测定单链和双链数量的洗脱技术 断裂和蛋白质到DNA的交联量 各种治疗方案。这些检查可能使我们能够 DNA水平上的损伤类型和损伤修复与数量 所看到的变化或突变。

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.