Cytokinetic effects of platinum (II) polyamines on three different cell lines using flow cytometry

The association between cytotoxicity and cell cycle perturbation caused by cisplatin and two platinum (II) polyamines, containing a methotrexate or a 2-chloro-p-phenylenediamine component, was investigated in human ovarian carcinoma cells (CAOV3), murine Balb 3T3 fibroblasts and Chinese ovarian hamster cells by flow cytometric DNA/protein, DNA/RNA and DNA degradation assays. Continuous in vitro drug exposure caused a time- and dose-dependent suppression of growth. Flow cytometric analysis revealed a multiplicity of cytokinetic perturbations, the most important of which was Go/G1 depletion and S phase arrest. The latter correlated with inhibition of DNA synthesis and subsequent inhibition of RNA and protein synthesis. Prolonged S phase arrest concomitant with DNA degradation, followed by RNA and protein degradation, resulted in cell death via apoptosis. The platinum polymers appear to be effective in vitro chemotherapeutic agents. The study of cytokinetic perturbations is useful in determining the relative potency of antitumor drugs and in monitoring drug effectiveness during treatment.