Durm M, Sorokine-Durm I, Haar F M, Hausmann M, Ludwig H, Voisin P, Cremer C
Institute of Applied Physics, University of Heidelberg, Germany.
Cytometry. 1998 Mar 1;31(3):153-62. doi: 10.1002/(sici)1097-0320(19980301)31:3<153::aid-cyto2>3.0.co;2-m.
Fluorescence in situ hybridization (FISH) has become a powerful tool in chromosome analysis. This report describes the systematic optimization of the Fast-FISH technique for centromere labeling of human metaphase chromosomes for radiobiological dosimetry purposes. For the present study, the hybridization conditions and the efficiency of two commercially available alpha-satellite DNA probes were compared ("human chromosome 1 specific", Oncor, Gaithersburg, MD, vs. "all-human chromosomes specific", Boehringer-Mannheim, Germany). These probes were hybridized to human lymphocyte metaphase plates by using a hybridization buffer without formamide and without any other equivalent denaturing chemical agents. The results indicate the suitability of the method for automated image analysis on the basis of thresholding. The optimal conditions concerning hybridization time and temperature were determined by a systematic quantitative evaluation of the fluorescent labeling sites after the hybridization procedures. Under defined "low stringency" conditions, we found that the "human chromosome 1 specific" DNA probe labeled not only the centromere of the human chromosome 1 but also the other human centromeres in the same way as the "all-human chromosome specific" DNA probe. The optimized conditions to complete all centromere labeling were applied to the detection of dicentric chromosomes on irradiated human lymphocyte samples (gamma-rays of 60Co source, 0.5 Gy/min, for doses of 1, 3, and 4 Gy). The yield of dicentrics was determined after Fast-FISH and compared with results obtained after Giemsa staining. These results are very compatible and indicate that, because of its simplicity, this optimized Fast-FISH procedure would be useful for fast screening purposes in biological dosimetry after accidental overexposure.
荧光原位杂交(FISH)已成为染色体分析中的一项强大工具。本报告描述了为放射生物学剂量测定目的,对用于人类中期染色体着丝粒标记的快速FISH技术进行的系统优化。在本研究中,比较了两种市售α-卫星DNA探针的杂交条件和效率(“人类1号染色体特异性”,Oncor公司,盖瑟斯堡,马里兰州,与“所有人类染色体特异性”,德国勃林格殷格翰公司)。这些探针通过使用不含甲酰胺且不含任何其他等效变性化学试剂的杂交缓冲液,与人类淋巴细胞中期板进行杂交。结果表明该方法适用于基于阈值的自动图像分析。通过对杂交程序后荧光标记位点的系统定量评估,确定了杂交时间和温度的最佳条件。在规定的“低严谨性”条件下,我们发现“人类1号染色体特异性”DNA探针不仅标记了人类1号染色体的着丝粒,还以与“所有人类染色体特异性”DNA探针相同的方式标记了其他人类着丝粒。将完成所有着丝粒标记的优化条件应用于受辐照人类淋巴细胞样本(60Co源γ射线,0.5 Gy/分钟,剂量为1、3和4 Gy)的双着丝粒染色体检测。在快速FISH后确定双着丝粒的产量,并与吉姆萨染色后获得的结果进行比较。这些结果非常吻合,表明由于其简单性,这种优化的快速FISH程序将有助于在意外过度暴露后的生物剂量测定中进行快速筛查。