Prolongation of G1 phase in cultured glioma cells by cis-dichlorodiammineplatinum (II) (CDDP): analysis using bromodeoxyuridine (BrdU)-Hoechst technique.

The cytokinetic response of three murine (AC) and human (GB-1 and GB-2) glioma cell lines to cisdichlorodiammineplatinum (II) (CDDP) was investigated by flow cytometry. Using the 5-bromodeoxyuridine (BrdU)-Hoechst technique, percentages of cultured glioma cells in the various phases of the cell cycle, and relative phase duration were calculated. This technique proved to be a rapid and easily performed method to characterize phase length and transition rate for the complete cell cycle. In the presence of CDDP IC10 (a concentration in which 10% inhibition of cell growth be induced as compared to controls), perturbations of the cell cycle in AC and GB-1 cells included G2 delay or block, decreased transit velocity from G1 to S phase, and prolongation of G1 phase. The mean cell cycle time increased 1.4 times in AC and 1.6 times in GB-1 as compared to controls. In CDDP IC 50-treated GB-2 cells, the mean cell cycle time was prolonged three times longer than control: however, duration of each phase could not be calculated because of significant perturbation of cell cycle. These results suggest that CDDP influences glioma cells at the G1/S boundary and in the G2 phase, resulting in prolongation of the G1 phase and, to a minor degree, in block of the G2 phase.