Differential induction of premature chromosome condensation by calyculin A in human fibroblast and tumor cell lines.
The feasibility of chemically-induced premature chromosome condensation (PCC) was tested in two human fibroblast and two human malignant melanoma cell lines. To induce PCCs, calyculin A, a potent protein phosphatase inhibitor, was used at a final concentration of 80 nM. Attached cells and cells put into suspension by trypsinization were incubated with calyculin A at 37 degrees C for 1 hour. Calyculin A was able to induce PCCs in all the phases of the cell cycle with the tumour cell lines giving the highest PCC frequency. No systematic differences were observed between attached cells and cells put into suspension by trypsinization. However, a cytotoxic effect that led to the loss of 50% to 80% of the treated cells was observed. The cytotoxic effect was more severe in the fibroblast than in the tumour cell lines. The appearance of deformed, fragile and fragmented nuclei with no particular chromatin condensation would explain to some extent this cytotoxic effect. A better understanding of the mechanism of action of calyculin A would help generalizing its use to study interphase chromosome aberrations.
Alsbeih
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Cancer Research Group, Ottawa Regional Cancer Centre, Canada.
Raaphorst
G P
GP
D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002877:Chromosomes, Human / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects / Q000648:ultrastructure; D006801:Humans; D008387:Marine Toxins; D010080:Oxazoles / Q000494:pharmacology*; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D008387:Marine Toxins; D010080:Oxazoles; C059041:calyculin A; D010749:Phosphoprotein Phosphatases