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.
Merlin
J L
JL
Laboratoire de Recherche en Oncologie, Centre Alexis Vautrin, Vandoeuvre-les-Nancy, France. jl.merlin@nancy.fnclcc.fr
Bour-Dill
C
C
Marchal
S
S
Bastien
L
L
Gramain
M P
MP
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects*; D004273:DNA, Neoplasm / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D004587:Electrophoresis, Agar Gel; D005260:Female; D006801:Humans; D008856:Microscopy, Fluorescence; D017239:Paclitaxel / Q000494:pharmacology*; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000972:Antineoplastic Agents, Phytogenic; D004273:DNA, Neoplasm; D017239:Paclitaxel