Ellard S, Toper S, Stemp G, Parry E M, Wilcox P, Parry J M
School of Biological Sciences, University of Wales Swansea, UK.
Mutagenesis. 1996 Nov;11(6):537-46. doi: 10.1093/mutage/11.6.537.
Chromosome aberrations induced by daunomycin, a widely used positive control compound for in vitro cytogenetics assays, were identified by multi-colour fluorescence in situ hybridization with probes for chromosomes 1, 2 and 3. The frequency and distribution of aberration types were compared to conventional metaphase analysis of Giemsastained chromosomes from parallel human lymphocyte cultures. Multi-colour chromosome painting was a more sensitive method for detecting daunomycin-induced chromosome aberrations compared with conventional metaphase analysis because: (i) a higher level of statistical significance was achieved at low doses; and (ii) the increases in aberration frequencies compared with controls were greater. The majority of exchanges identified by Giemsastaining were unstable and were likely to lead to cell death. In contrast, those detected by FISH were mostly stable exchanges which may be transmitted to cell progeny. Multicolour FISH using whole chromosome probes may provide an elegant solution to the problem of identifying non-lethal, heritable exchange events. The benefit of this technique is the quantification of a cytogenetic endpoint directly associated with carcinogenesis.
柔红霉素是体外细胞遗传学检测中广泛使用的阳性对照化合物，通过用1号、2号和3号染色体探针进行多色荧光原位杂交来鉴定其诱导的染色体畸变。将畸变类型的频率和分布与来自平行人类淋巴细胞培养物的吉姆萨染色染色体的传统中期分析进行比较。与传统中期分析相比，多色染色体描绘是检测柔红霉素诱导的染色体畸变更灵敏的方法，原因如下：（i）在低剂量时能达到更高水平的统计学显著性；（ii）与对照相比，畸变频率的增加更大。吉姆萨染色鉴定出的大多数交换是不稳定的，可能导致细胞死亡。相比之下，荧光原位杂交检测到的大多是稳定交换，可能会传递给细胞后代。使用全染色体探针的多色荧光原位杂交可能为识别非致死性、可遗传交换事件的问题提供一个优雅的解决方案。这项技术的好处是对与致癌作用直接相关的细胞遗传学终点进行定量。
