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 MCF7(TAX19) paclitaxel-r esistant subline exposed to paclitaxel for 24 h. No nucleosome-sized DNA fr agmentation was observed by DNA agarose gel electrophoresis in both cell li nes. However, DNA fragmentation was detected by flow cytometry sub-G(1) pea k analysis in both cell lines immediately after paclitaxel exposure. Nuclea r 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 differenc es were observed between sensitive and resistant cell lines, 24 h after exp osure to 50 nmol/l paclitaxel. Although no difference in the sub-G(1) cell population was observed between sensitive and resistant cells, a significan tly higher rate of multinucleated cell features was observed in resistant c ells. [(C) 2000 Lippincott Williams & Wilkins.].