Development of polyploidization in taxol-resistant human leukemia cells in vitro.
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.
Roberts
J R
JR
Department of Surgery, Johns Hopkins Hospital, Baltimore, MD 21205.
Allison
D C
DC
Donehower
R C
RC
Rowinsky
E K
EK
D000470:Alkaloids / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D004273:DNA, Neoplasm / Q000378:metabolism; D004351:Drug Resistance; D006801:Humans; D007399:Interphase / Q000187:drug effects; D007938:Leukemia / Q000503:physiopathology*; D017239:Paclitaxel; D011123:Polyploidy; D008941:Spindle Apparatus / Q000187:drug effects; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000470:Alkaloids; D004273:DNA, Neoplasm; D017239:Paclitaxel