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

Cytometry. 1992;13(4):416-22. doi: 10.1002/cyto.990130412.


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 a colony formation assay, under all treatment conditions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / pathology*
  • Bromodeoxyuridine*
  • Cell Cycle / drug effects*
  • Cisplatin / pharmacology*
  • DNA Damage
  • DNA, Neoplasm / analysis*
  • DNA, Neoplasm / drug effects
  • Flow Cytometry / methods*
  • Fluorescent Antibody Technique*
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology*
  • Tumor Cells, Cultured / chemistry
  • Tumor Cells, Cultured / drug effects
  • Tumor Stem Cell Assay


  • DNA, Neoplasm
  • Bromodeoxyuridine
  • Cisplatin