Wortmannin selectively enhances radiation-induced apoptosis in proliferative but not quiescent cells.
OBJECTIVE
To examine whether wortmannin enhances radiation-induced apoptosis in human lymphoid cells.


METHODS
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.


CONCLUSIONS
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.
Shi
Y Q
YQ
Division of Radiation Medicine, Biosciences Department, Paul Scherrer Institute, Villigen, Switzerland.
Blattmann
H
H
Crompton
N E
NE
D000730:Androstadienes / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000528:radiation effects; D002455:Cell Division; D002478:Cells, Cultured / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005434:Flow Cytometry; D006801:Humans; D008856:Microscopy, Fluorescence; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000528:radiation effects; D000077191:Wortmannin
D000730:Androstadienes; D011838:Radiation-Sensitizing Agents; D000077191:Wortmannin