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Wortmannin selectively enhances radiation-induced apoptosis in proliferative but not quiescent cells
Y Q Shi1, H Blattmann, N E Crompton
1Division of Radiation Medicine, Biosciences Department, Paul Scherrer Institute, Villigen, Switzerland.
Purpose:
To examine whether wortmannin enhances radiation-induced apoptosis in human lymphoid cells.
Methods And Materials:
Different concentrations of wortmannin (0-40 micrOM) were added to TK6 lymphoblastoid cell and whole blood cell cultures 15 min before irradiation (0-6-Gy X-rays). After irradiation, medium was changed and cells were left to incubate for 48 h. In blood samples, CD4, CD8, and CD20 lymphocytes were labeled using FITC-conjugated antibodies. All cell types were fixed in a diethyleneglycol-formaldehyde solution. DNA was stained with propidium iodide. Apoptosis was quantified using flow cytometry and confirmed using fluorescence microscopy.
Results:
Wortmannin significantly enhances radiation-induced apoptosis in lymphoblastoid cells. Compared to the controls, wortmannin treatment only slightly enhanced radiation-induced apoptosis in quiescent T-lymphocytes and had no effect in quiescent B-lymphocytes.
Conclusion:
Wortmannin enhances radiation-induced apoptosis in a cell-type dependent manner. If the selective effect of wortmannin on proliferative tissues also exists in nonlymphoid tissues, it should enhance the therapeutic ratio of treatments for tumors located in poorly proliferative healthy tissues. Further studies are needed to compare the effects of wortmannin in human tumor cells and various normal cells including proliferative and quiescent cells.