BrdUrd/DNA flow cytometry analyses demonstrates cis‐diamminedichloroplatinum (II)‐induced multiple cell‐cycle modifications on human lung carcinoma cells

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Abstract
The treatment of cultured human cells by cis‐diamminedichloroplatinum (II) (cis‐DDP) has been shown to induce complex modifications in the cell cycle. Using dual parameter DNA/BrdUrd flow cytometric analysis, we were able to monitor the cell cycle traverse of a pulse‐labeled cohort of cells in an asynchronous culture of the A549 cell line (human lung adenocarcinoma). Two major modifications of the cell cycle following cis‐DDP treatment were observed: (1) after 24 h of treatment, the labeling index was significantly increased and was linked with a prolonged S‐phase; the S‐phase delay occurred rapidly after cis‐DDP and was dose dependent but not exposure time dependent; (2) an accumulation of cells at the S/G2 transition with an onset approximately 12 h after cis‐DDP contact, which was found to be dependent on both dose and duration of exposure. The cytokinetic results also predict maximal sensitivity to cis‐DDP for G1 cells and minimal for G2 cells. In our model the late S/G2 accumulation was always preceded by a slowing down of the S‐phase. However, only the former should be the correct indicator of cytotoxicity since it was correlated with cell survival as evidenced by d colony formation assay, under all treatment conditions.