NEUTRON DOSE PROTRACTION EFFECT ON TRANSFORMATION

本应用程序长期目标是定义并开始 为了寻求对增强效果的理解， 在低剂量和剂量率下暴露于中子会导致这种 作为肿瘤转化和突变的终点。在……里面 特别是，这项研究将在细胞水平上定义能量 对这一现象的依赖既是为了获得更多的知识 生物物理限制决定了影响和 确定对暴露于此的人类的风险是否仅限于 职业上暴露在裂变中子或更广泛的光谱中 可能暴露在中子和其他高强度气体中的人 各种能量的辐射。为了做到这一点，具体的 这项计划的目标是： 1.更清楚地定义增强型能源的依赖 长期暴露于低剂量苯系物的致癌作用 中子。 2.对突变克隆的DNA进行分子分析 通过将细胞暴露在各种能量的中子中而产生的。 3.确定链断裂修复的作用和 细胞暴露于空气中而产生的未修复断裂的意义 不同能量的中子。 4.检验低剂量率中子具有 “类似于发起人”的特性。 5.检验以下假设：一种容易出错的修复形式可能 同时参与病变的产生和表达 这会导致增强的效果。 利用加州大学洛杉矶分校回旋加速器产生的质子 在46、30、20和12 MeV的铍，以下主要 在啮齿动物和人类细胞 暴露于急性和/或长期暴露：肿瘤 C3H10T1/2细胞转化、HGPRT和HGPRT突变 V79、转化人P3和/或正常人IMR中的TK基因座 91细胞，DNA单双链断裂产生，其修复 和修复的保真度以及最终的限制性片段分析 从突变克隆的DNA中确定缺失是什么 类型和模式。

The long term objective of this application is to define and begin to search for an understanding of the enhanced effects that exposures to neutrons at low doses and doses rates cause on such endpoints as neoplastic transformation and mutation. In particular, the study will define at the cell level the energy dependence of this phenomenon both to gain more knowledge of the biophysical limitations determining the effects and to determine if the risks to humans exposed are confined to those occupationally exposed to fission neutrons or to a wider spectrum of people who may be exposed to neutons and other high LET radiations of various energies. In order to do this, the specific aims of the project are: 1. To define more clearly the energy dependence of enhanced carcinogeneic effects at low doses with protracted exposures to neutrons. 2. To make a molecular analysis of DNA from mutant clones produced by exposing cells to neutrons of various energies. 3. To define the role of repair of strand breaks and the significance of unrepaired breaks produced by exposure of cells to neutrons to various energies. 4. To test the hypothesis that low dose rate neutrons have "promoter-like" properties. 5. To test the hypothesis that a form of error-prone repair may be involved in both the production and the expression of lesions that cause the enhanced effects. Using neutrons produced at the UCLA cyclotron from protons on Beryllium at 46, 30, 20, and 12 MeV, the following major endpoints will be measured after rodent and human cells are exposed to acute and/or protracted exposures: Neoplastic transformation in C3H10T1/2 cells, mutation at the HGPRT and TK loci in V79, transformed human P3 and/or normal human IMR- 91 cells, DNA single and double strand break production, its repair and fidelity of the repair and finally restriction fragment analysis of DNA from mutant clones to determine what are the deletion types and patterns.