Taxol-induced polyploidy and cell death in CHO AA8 cells

Abstract

The purpose of this study was to assess whether Taxol-induced changes in microtubular dynamics are accompanied by apoptosis. CHO AA8 cells were treated with different Taxol concentrations (0.25microM, 0.5microM, 1microM) for 24h. The effects of Taxol exposure were analyzed using fluorescence microscopy and flow cytometry (TUNEL and annexin V-FITC/propidium iodide assays). 0.25microM Taxol caused the appearance of few multinucleated giant cells exhibiting extensive arrays of fine filaments. Slight increases in the level of polyploidy, phosphatidylserine externalization and in the percentage of TUNEL positive cells were noticed. Concentrations of 0.5 and 1microM resulted in the appearance of a large number of giant cells, which exhibited, depending on the cell, an extensive microtubular network or loose or tightly packed bundles of microtubules. Cells of reduced volume and showing chromatin condensation were also seen. Cell cycle analysis revealed that almost half of the cell population was polyploid. Except in cells exposed to 1microM Taxol, annexin V-FITC/PI labelling did not reveal the loss of plasma membrane integrity or increase in phosphatidylserine externalization; however, TUNEL assay revealed a significant increase in the percentage of cells with DNA fragmentation. These data indicate that CHO AA8 cells treated with Taxol undergo cell death of a type which considerably differs from apoptosis.