Development of polyploidization in taxol-resistant human leukemia cells in vitro.

Abstract

The effects of taxol on antitubulin immunofluorescent staining patterns, cellular DNA content, and labeling with [3H]thymidine were measured for the taxol-sensitive HL60 and taxol-resistant K562 cell lines after exposures for 0, 4, 12, and 24 h. Taxol caused a relative increase in the fraction of 4C interphase and metaphase cells in both lines although the 4C interphase accumulation was greater for the resistant K562 line. Of the cells with S-phase DNA content, taxol-treated HL60 cells were less likely to incorporate [3H]thymidine than taxol-treated K562 cells. However, a decrease in percentage of S-phase labeling for both lines relative to control cells was seen. Finally, taxol induced the development of polyploid cells (cells with DNA contents greater than that of the 4C G2-M peak) in the relatively taxol-resistant K562 cells, an effect not seen in the relatively taxol-sensitive HL60 line. After 24 h of taxol exposure 70% of all K562 cells were polyploid while only 8% of the HL60 cells were polyploid. The capacity of K562 cells to generate polyploidy in response to taxol correlated with taxol resistance by previous assay and may be a useful indicator of drug resistance.