Resistance to paclitaxel induces time-delayed multinucleation and DNA fragmentation into large fragments in MCF-7 human breast adenocarcinoma cells.

DNA fragmentation was investigated in MCF7 and the MCF7TAX19 paclitaxel-resistant subline exposed to paclitaxel for 24 h. No nucleosome-sized DNA fragmentation was observed by DNA agarose gel electrophoresis in both cell lines. However, DNA fragmentation was detected by flow cytometry sub-G1 peak analysis in both cell lines immediately after paclitaxel exposure. Nuclear abnormalities were observed in both cell lines in the range of 35-40% of the total cell population. This value was reached immediately in MCF7 cells but was time-delayed in MCF7TAX19 cells. Significant morphologic differences were observed between sensitive and resistant cell lines, 24 h after exposure to 50 nmol/l paclitaxel. Although no difference in the sub-G1 cell population was observed between sensitive and resistant cells, a significantly higher rate of multinucleated cell features was observed in resistant cells.