HUMAN SOMATIC CELL MUTAGENESIS BY GAMMA RAYS

电离辐射是否可通过基因内(或 “点”)突变是不确定的。来自研究的证据，使用 动物和细胞表明大部分或全部电离辐射诱变 是由于染色体异常，而不是基因内突变。这个 电离辐射有可能引起基因内辐射的假说 突变将使用培养的人类成纤维细胞、淋巴细胞和 上皮样细胞和哇巴因抗性作为生化标记物。这个 哇巴因耐药性的诱导被认为是通过体内的突变 膜离子转运蛋白Na+K+ATPase的哺乳动物基因 受这种药物的影响。迄今为止的研究，基于后辐射 选择能够在哇巴因治疗后存活并形成克隆的细胞， 没有证据表明这种突变可以由电离引起 辐射。因此，拟议的研究将寻求对哇巴因具有抗药性。 通过一种更敏感、更不依赖生存的技术突变细胞： 激光激活的细胞分选。哇巴因对γ-射线照射的影响 对照细胞将使用荧光染料进行测量， 膜电位，以及未受影响的细胞将被分类和分析 后天的和可遗传的哇巴因抵抗。如果这样的数量增加 细胞在伽马射线照射的培养中发生基因内突变的估计 入门费率将首次开放。

Whether ionizing radiation can induce mammalian mutations by intragenic (or "point") mutation is not known with certainty. Evidence from studies using animals and cells indicates that most or all ionizing radiation mutagenesis is due to chromosomal aberration and not intragenic mutation. The hypothesis that it is possible for ionizing radiation to cause intragenic mutation will be tested using cultured human fibroblasts, lymphocytes, and epithelioid cells and ouabain resistance as biochemical marker. The induction of ouabain resistance is thought to be through a mutation within the mammalian gene for Na+K+ATPase, the membrane ion-transport protein afftected by this drug. Research to date, based on the post-irradiation selection of cells that can survive ouabain treatment and form colonies, has shown no evidence that this mutation can be caused by ionizing radiation. The proposed research will therefore seek ouabain-resistant mutant cells by a more sensitive and less survival-dependent technique: laser-activiated cell sorting. The effect of ouabain on gamma-irradiated and control cells will be measured using fluorescent dyes that measure membrane potential, and unaffected cells will be sorted and analysed for acquired and heritable ouabain resistance. If an increased number of such cells occurs in gamma-irradiated cultures an estimate of intragenic mutaton inducation rate will be available for the first time.