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MUTATION-TRANSFORMATION: NEUTRON DAMAGE AND REPAIR

突变转化：中子损伤与修复

基本信息

批准号：
3171723
负责人：
ELIEZER HUBERMAN
金额：
$ 21.98万
依托单位：
UNIVERSITY OF CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
1983
资助国家：
美国
起止时间：
1983-02-01 至 1989-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3171723
关键词：
DNA repair X ray gamma radiation gene mutation hamsters ionizing radiation linear energy transfer mutagens neutron radiation radiation carcinogenesis radiation dosage radiation genetics radiation related neoplasm /cancer radiation sensitivity radiobiology relative biological effectiveness tissue /cell culture

项目摘要

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.

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。