BrdUrd/DNA flow cytometry analysis demonstrates cis-diamminedichloroplatinum (II)-induced multiple cell-cycle modifications on human lung carcinoma cells.
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.
Demarcq
C
C
Laboratoire de Pharmacocinétique, Institute Curie, Paris, France.
Bastian
G
G
Remvikos
Y
Y
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology*; D001973:Bromodeoxyuridine; D002453:Cell Cycle / Q000187:drug effects*; D002945:Cisplatin / Q000494:pharmacology*; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000032:analysis* / Q000187:drug effects; D005434:Flow Cytometry / Q000379:methods*; D005455:Fluorescent Antibody Technique; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology*; D014407:Tumor Cells, Cultured / Q000737:chemistry / Q000187:drug effects; D014410:Tumor Stem Cell Assay
D004273:DNA, Neoplasm; D001973:Bromodeoxyuridine; D002945:Cisplatin