G. Sena et al., Measuring the complexity of cell cycle arrest and killing of drugs: Kinetics of phase-specific effects induced by Taxol, CYTOMETRY, 37(2), 1999, pp. 113-124
Background: Paclitaxel (Taxol) is known to act mainly in mitosis, interferi
ng with microtubule dynamics, but effects on the other cells cycle phases h
ave been reported also. However, a comparative picture of perturbation and
killing in the G(1), S and G(2)M phases after drug treatment is lacking. Th
e approach developed by our group tackles the problem of the complexity of
cell cycle effects with the aid of a computer program simulating cell cycle
progression and new quantities measuring cell-cycle arrest and death.
Methods: The program generates data that were compared with those given by
absolute cell counts and by different flow cytometry techniques, enabling u
s to follow the fate of G1 and G2M blocked cells either re-entering the cyc
le or dying, distinguishing cytostatic and cytotoxic effects. Apoptosis was
analyzed in order to refine the description of cytotoxic effects.
Results: We estimated the number of blocked and dead cells after short-term
Taxol treatments in a range of concentrations and post-drug incubation tim
es. G2M block was immediately active at low concentrations but was reversib
le, becoming irreversible only at the highest concentrations. G1 block beca
me active later, allowing cell cycle progression of cells initially in G1,
but was still active 48 h post-treatment, at intermediate concentrations. S
-phase delay was detected after 24 h. The death rate was much higher within
G1 than G2M blocked cells.
Conclusions: Our analysis unraveled the complexity of cell cycle effects of
the drug, and revealed the activity of G1 checkpoint, hidden by a prompter
but less cytotoxic G(2)M block. Cytometry 37:113-124, 1999. (C) 1999 Wiley
-Liss, Inc.