Cyclosporin A antileukemic activity: mode of action on target cells

Cyclosporin A (CyA) is a potent immunosuppressive agent which has been reported to inhibit proliferation of human T leukemic lymphoblasts. We used the permanent cell line 8402 to perform a detailed investigation of the CyA mode of action on such cells. CyA treatment resulted in a dose-dependent inhibition of the 8402 cells growth rate which was paralleled by a decrease of tritiated thymidine uptake. These findings were the consequence of redistribution of treated cells in the cell cycle phase. By means of intracellular DNA content measurements made by flow cytometry, it was shown that the primary effect of CyA was accumulation of treated cells at the G1 phase of the cell cycle. At the doses used, CyA activity was not spontaneously reversible, resulting in death of treated cells which was apparent at about 72 h after exposure to the drug.