CYTOGENETIC EFFECTS PERTAINING TO LOW DOSES OF RADIATION

本申请中提出的研究的长期目标是 阐明了一些参与染色体产生的机制， 电离辐射暴露后的畸变，因为它们与 低水平辐射危害的评估，以及与 这些细胞杀伤与放射治疗癌症更相关。 更具体地，所提出的实验被设计为测试 修复饱和模型对各种曲线的解释能力 生物剂量反应稀疏电离辐射，以及提供 关于经常预算开支/地方预算开支关系的性质的资料。将采取的办法 用于实现这些目标的资源概述如下： 1. 利用早熟染色体凝聚技术， 将测量染色体断裂重新连接率作为剂量的函数 递送至静止的正常人成纤维细胞。这一比率的下降， 在与存活“肩”区相关的剂量范围内 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 一起，应该可以确定是否交换畸变， 发生在受损和未受损的染色质之间，当合胞体到达 下一个有丝分裂预计这种交换将在 某些修复饱和模型的假设。 3. 人类间期染色体（PCC）对初始辐射的剂量反应 将研究由α粒子引起的断裂，以及 这些损伤被细胞重新连接的速度。结果的对比 这些研究与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伤本来就不易修复， 修复饱和模型通常保持不变。 4. 提出了PCC方法的进一步改进，特别是 明确鉴定G 0/G1 PCC的着丝粒区域的能力。这 可以精确测量辐射引起的染色体断裂 是由远低于10拉德的剂量引起的

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.