RADIOSENSITIVE TARGET IN THE EARLY MOUSE EMBRYO

小鼠胚胎嵌合体试验是一种非常敏感的检测 将哺乳动物生殖细胞活体暴露在电离辐射下。这 暴露产生竞争性胚胎细胞增殖劣势 当来自暴露的双亲的胚胎表达时 通过与聚集中的对照胚胎的细胞-细胞接触来挑战 奇美拉。该方法对低LET电离辐射的检出限 (伽马或X射线)对亲本男性来说在0.005-0.01Gy之间 双亲女性的照射剂量在0.05~0.15 Gy之间 辐射。在当前的资助期内，我们成功地 实现我们的主要目标，那就是确定 放射增敏靶点为核或核外。这个 我们获得的证据有力地支持了原子核的假说 在这个竞争激烈的续订应用中，我们现在希望 来测试关于这一损害可能造成的后果的假设 核靶向及嵌合体检测对人类免疫缺陷的预测价值 利用核端点传递胚胎效应。 特定目标1将检验该核目标包括 通过影响细胞增殖而影响细胞增殖率的 生长因子/受体自分泌效率“环”。这一假设是 基于已知的几个功能自分泌循环的表达式 早期胚胎和越来越多的证据表明，生长因子， 它们的受体，相关的信号转导组件和 转录因子在多种细胞系中具有辐射敏感性。 还有纸巾。 具体目标2和3涉及的是 嵌合体试验检测双亲接触铅对胚胎的影响 电离辐射。与特定目标1的情况一样，假设 这里测试的是基于对核辐射敏感的目标 嵌合体试验。《特定目标2》将检验高剂量的假设 对雌性生殖细胞系(0.3Gy0.5Gy137Cs伽马辐射)会 导致嵌合体阳性结果之间的时间相关性 检测和传递发育增加的卵子发生阶段 文献中报告的异常(例如，特定轨迹测试)。 具体目标3将检验假设，即将有时间 嵌合体检测的阳性结果与增加之间的相关性 在他们的生殖细胞中检测到的染色体畸变率 男性的荧光原位杂交。

The mouse embryo chimera assay is a very sensitive test for detecting in vivo exposure of the mammalian germ cell to ionizing radiation. This exposure produces a competitive embryonic cell proliferation disadvantage that becomes expressed by the embryo from the exposed parent when challenged by cell-cell contact with a control embryo in an aggregation chimera. The detection limits of this assay for low-LET ionizing radiation (gamma or x rays) are between 0.005 Gy and 0.01 Gy for parental male irradiation and between 0.05 Gy and 0.15 Gy for parental female irradiation. During the current funding period we were successful in achieving our major objective, which was to determine whether the radiosensitive target for the assay was nuclear or extranuclear. The evidence we obtained strongly favors the hypothesis for a nuclear radiosensitive target in this competitive renewal application, we now wish to test hypotheses regarding the possible consequences of damage to this nuclear target and the predictive value of the chimera assay for transmitted embryonic effects using nuclear endpoints. Specific Aim 1 will test the hypothesis that this nuclear target consists of genes that affect cell proliferation rate through their impact on the efficiency of growth factor/receptor autocrine "loops". This hypothesis is based upon the known expression of several functional autocrine loops by the early embryo and on the accumulating evidence that growth factors, their receptors, associated signal transduction components and transcription factors are radiosensitive in a wide variety of cell lines and tissues. Specific Aims 2 and 3 are concerned with the predictive value of the chimera assay for embryonic effects resulting from parental exposures to ionizing radiation. As is the case for Specific Aim 1, the hypotheses tested here are predicated upon a nuclear radiosensitive target for the chimera assay. Specific Aim 2 will test the hypothesis that higher doses to the female germ line (0.3 Gy - 0.5 Gy of 137 Cs gamma radiation) will result in a temporal correlation between positive results of the chimera assay and the stages of oogenesis that transmit increases in developmental anomalies as reported in the literature (e.g., the specific locus test). Specific Aim 3 will test the hypothesis that there will be temporal correlations between positive results from the chimera assay and increases in frequencies of chromosomal aberrations detected in their germ cells by fluorescence in situ hybridization in males.