Characterization of alkylating versus intercalating anticancer drug-induced effects on cell survival, cell cycle kinetic and morphonuclear pattern of three neoplastic cells lines growing in vitro

Abstract

Purpose: 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.

Methods: This monitoring was carried out by means of the digital cell image analysis of Feulgen-stained nuclei.

Results: 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.

Conclusions: 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.