CYTOGENETIC EFFECTS PERTAINING TO LOW DOSES OF RADIATION

本申请中提出的研究的长期目标是 阐明一些与染色体产生有关的机制 暴露于电离辐射后的像差，因为它们与 评估低水平辐射危害，以及与以下方面相关的进程 与放射治疗癌症治疗更相关的细胞杀伤。 更具体地说，拟议的实验旨在测试 修复-饱和模型解释各种曲线的合理性 生物剂量-对稀疏电离辐射的反应，以及提供 关于RBE/LET关系性质的信息。将采取的方法是 用来实现这些目标的概述如下： 1.利用染色体过早凝集(PCC)技术， 染色体断裂重组率将作为剂量的函数进行测量 被输送到静止的正常人类成纤维细胞。这一比率的下降， 超过与“肩部”生存区域相关的剂量范围 响应，将被解释为修复饱和的证据 细胞遗传学水平。 2.通过立即融合辐照和未辐照的有丝分裂CHO细胞 总之，应该有可能确定交换像差是否 发生在受损和未受损染色质之间，当合胞体到达 下一个有丝分裂。这种交流预计将发生在 对某些修复饱和模型的假设。 3.人间期染色体(PCC)对初始剂量的反应 将研究由阿尔法粒子造成的破缺，以及 这些病变被细胞重新连接的速率。比较以下各项的结果： 这些对使用伽马射线获得的研究将表明 高密度电离辐射造成的损害天生就不太容易修复，因为 修复-饱和模型通常保持不变。 4.建议进一步改进PCC方法，特别是 明确识别G0/G1PCC着丝粒区域的能力。这 将允许准确测量辐射引起的染色体断裂 由远低于10rad的剂量引起。

The long-term goals of the research proposed in this application are to elucidate some of the mechanisms involved in the production of chromosomal aberrations following exposure to ionizing radiation as they pertain to both the assessment of low-level radiation hazards, and processes associated with cell killing that are more pertinent to cancer treatment by radiotherapy. More specifically, the proposed experiments are designed to test the plausibility of repair-saturation models in explaining various curvilinear biological dose-responses to sparsely ionizing radiation, as well as provide information on the nature of RBE/LET relationships. The approaches to be used in achieving these goals are outlined as follows: 1. Utilizing the technique of premature chromosome condensation (PCC), the rate of chromosome break rejoining will be measured as a function of dose delivered to quiescent normal human fibroblasts. A decrease in this rate, over the dose range associated with the "shoulder" region of survival response, will be interpreted as evidence of repair-saturation at the cytogenetic level. 2. By immediately fusing irradiated and unirradiated mitotic CHO cells together, it should be possible to determine whether exchange aberrations occur between damaged and undamaged chromatin, when the syncytia reach the next mitosis. Such exchanges would be predicted to occur under the assumptions of certain repair-saturation models. 3. The dose response of human interphase chromosomes (PCC) to initially produced breaks caused by alpha-particles will be studied, as well as the rate at which these lesions are rejoined by cells. Comparing the results of these studies to those obtained using gamma-rays will indicate whether damage from densely ionizing radiation is inherently less repairable, as repair-saturation models generally maintain. 4. Further improvements in PCC methodology are proposed, specifically the ability to unequivocally identify the centromeric regions of G0/G1 PCC. This would allow the accurate measurement of radiation-induced chromosome breaks caused by doses well below 10 rad.