Time-lapse studies on the effect of vincristine on HeLa cells

Phase-contrast time-lapse studies on the effect of vincristine (VCR) on HeLa cells have been carried out with different VCR doses (0.0025; 0.005; 0.03 μg/ml) and different incubation times (continuous and 0.5, 1, 3, 12hr). Type and extent of cell damage depend on the applied dose/exposure time relation and on the position of the cells within the cell cycle during VCR treatment. Continuous incubation results in mitotic arrest and subsequent necrosis of all cells entering mitosis, even at VCR concentrations as low as 0.005 μg/ml. The fate of short-term treated cells depends on the time of entry into mitosis. All cells entering mitosis during the first 8 hr after drug removal are lethally or sublethally damaged; later on regular mitoses also occur. Using cinematography it could be shown directly that VCR-arrested mitoses are no longer capable of further regular proliferation. However, VCR does not only cause lethal cell damage, i.e., necrosis after mitotic arrest, but also sublethal damage leading to pathological divisions after mitotic arrest, with descendants not capable of regular proliferation.