Pauwels O, Kiss R, Pasteels J L, Atassi G
Laboratoire de Pharmacologie Cellulaire, Université Libre de Bruxelles, Belgium.
Pharm Res. 1995 Jul;12(7):1011-8. doi: 10.1023/a:1016258431063.
The influence of three alkylating and three intercalating anticancer drugs on cell survival, cell cycle kinetics and chromatin patterns was monitored in vitro on three neoplastic cell lines.
This monitoring was carried out by means of the digital cell image analysis of Feulgen-stained nuclei.
Results show that in term of cytotoxicity, the intercalating drugs were more potent than the alkylating ones. As for the cell kinetics assessment, most of the experimental conditions led to a blockage of the cells in the G2 phase of the cell cycle. A study of chromatin patterns by means of digital cell image analysis enabled us to describe 15 morphonuclear parameters. The results show that the drugs tested induced specific morphonuclear modifications, e.g. an increase in nuclear size. The 15 morphonuclear parameters were submitted to multivariate analyses, i.e. principal-components analyses followed by the canonical transformation of the data. The results of these multivariate analyses enabled us to discriminate between the alkylating and the intercalating drugs.
We conclude that it would be possible to "diagnose" the mechanism of action of DNA interacting agents (alkylating or intercalating drugs) by means of the combination of digital cell image and multivariate analysis.
在三种肿瘤细胞系上，体外监测三种烷化剂和三种嵌入型抗癌药物对细胞存活、细胞周期动力学和染色质模式的影响。
通过对福尔根染色细胞核进行数字细胞图像分析来进行这种监测。
结果表明，在细胞毒性方面，嵌入型药物比烷化剂更有效。至于细胞动力学评估，大多数实验条件导致细胞在细胞周期的G2期受阻。通过数字细胞图像分析对染色质模式进行研究，使我们能够描述15个形态核参数。结果表明，所测试的药物诱导了特定的形态核改变，例如核大小增加。对这15个形态核参数进行多变量分析，即主成分分析，随后对数据进行典型变换。这些多变量分析的结果使我们能够区分烷化剂和嵌入型药物。
我们得出结论，通过数字细胞图像和多变量分析相结合，有可能“诊断”DNA相互作用剂（烷化剂或嵌入型药物）的作用机制。
