RADIATION CYTOGENETICS

在高等真核细胞中， 主要参与了所有重要的生物效应 电离辐射，包括细胞繁殖死亡， 放射治疗癌症的核心， 对人类的主要危害来自低水平的 电离辐射暴露。 该项目的目标是 更好地理解畸变的机制 形成;确定和描述影响类型的因素 和辐射产生的畸变频率;以及 探索和发展新的方法， 测量低水平辐射照射的遗传效应。 具体来说，我们的目标集中在病变性质的研究 导致畸变形成， 间期染色体断裂表现为过早 浓缩染色体（PCC）以及有丝分裂染色体。 将在与其他药物治疗后进行比较， 产生DNA双链的电离辐射 休息. 将开展进一步的具体研究， 确定间期染色体是否断裂 优先在常染色质或异染色质中， 紫外线和X射线引起的中期畸变主要发生在 一个或另一个在田鼠grestus细胞与巨大的 异染色质性染色体 抑制作用的研究 X射线诱导的PCC断裂的重新连接或表达增加 使用非等渗盐、阿糖胞苷和咖啡因治疗， 应强调影响之间的关系， 观察到PLD和SLD“修复”。 此外，研究将 在杂交细胞中进行互补， 来自共济失调-毛细血管扩张症患者的细胞;首先，观察 是否导致染色单体畸变产生的缺陷 从G1 X射线照射可以纠正互补， 杂交，第二，以确定染色体的位置， 一种能纠正导致过敏的缺陷的人类基因 在CHO细胞的X射线敏感突变体中。 最后，我们将 尝试测量X射线诱导的染色体异常， 比以前更高的分辨率和更高的灵敏度 已经可能，使用EM制剂的联会复合体的 粗线期早期小鼠精母细胞。 该项目的目标和宗旨对 癌症放射治疗的科学基础， 低水平的遗传和致癌危险的评价 电离辐射暴露。

In higher eukaryotic cells, chromosomal aberrations are principally involved in all of the important biological effects of ionizing radiations, including cell reproductive death that is central to cancer therapy by radiation, and oncogenesis that is the principal hazard to the human population from low level ionizing radiation exposure. The goals of this project are to gain a better understanding of the mechanisms of aberration formation; to identify and characterize factors influencing types and frequencies of aberrations produced by radiation; and to explore and develop new approaches to the quantitative measurement of genetic effects of low level radiation exposure. Specifically our aims focus on studies of the nature of lesions that lead to aberration formation including an investigation of interphase chromosome breakage as expressed in prematurely condensed chromosomes (PCCs) as well as mitotic chromosomes. Comparisons would be made following treatment with agents other than ionizing radiation that also produce DNA double strand breaks. Further specific studies would be carried out to determine whether interphase chromosome breakage occurs preferentially in euchromatin or heterochromatin and whether metaphase aberrations from U.V. and x-rays occur predominantly in one or the other in Microtus agrestus cells with giant heterochromatic sex chromosomes. Studies on the inhibition of rejoining or increased expression of x-ray induced PCC breaks using anisotonic salt, ara-A, and caffeine treatments would also be undertaken with emphasis on the relationship of the effects observed to PLD and SLD "repair". In addition, studies would be undertaken on the complementation in hybrid cells of a defect in cells from patients with Ataxia-Telangiectasia; first, to see whether the defect resulting in chromatid aberration production from G1 x-irradiation can be corrected by complementation in hybrids, and second to determine the chromosomal location of a human gene that corrects the defect leading to hypersensitivity in an x-ray sensitive mutant of CHO cells. Lastly, we would attempt to measure x-ray induced chromosomal abnormalities with higher resolution and greater sensitivity than has previously been possible, using EM preparations of synaptonemal complexes of early pachytene mouse spermatocytes. The goals and aims of this project are important for the scientific underpinning of cancer radiotherapy and for a fuller appreciation of genetic and oncogenic hazards of low level ionizing radiation exposure.