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Here we found that wortmannin sensitized Chinese hamster V79 cells to hyperthermic treatment at 44.0 degrees C as determined either by colony formation assay or by dye exclusion assay. Wortmannin enhanced heat-induced cell death accompanying cleavage of poly (ADP-ribose) polymerases (PARP). Additionally, the induction of heat shock protein HSP70 was suppressed and delayed in wortmannin-treated cells. Heat sensitizing effect of wortmannin was obvious at more than 5 or 10 microM of final concentrations, while radiosensitization was apparent at 5 microM. Requirement for high concentration of wortmannin, i.e., order of microM, suggests a possible role of certain protein kinases, such as DNA-PK and/or ATM among PI3-kinase family. The sensitization was minimal when wortmannin was added at the end of heat treatment. This was similar to the case of X-ray. Since heat-induced cell death and PARP cleavage preceded HSP70 induction phenomenon, the sensitization to the hyperthermic treatment was considered mainly caused by enhanced apoptotic cell death rather than secondary to suppression or delay by wortmannin of HSP70 induction. Further, in the present system radiosensitization by wortmannin was also at least partly mediated through enhancement of apoptotic cell death.
M Tomita, and
N Suzuki, and
Y Matsumoto, and
K Hirano, and
N Umeda, and
K Sakai
December 1988,
Journal of radiation research,
M Tomita, and
N Suzuki, and
Y Matsumoto, and
K Hirano, and
N Umeda, and
K Sakai
January 2002,
Teratogenesis, carcinogenesis, and mutagenesis,
M Tomita, and
N Suzuki, and
Y Matsumoto, and
K Hirano, and
N Umeda, and
K Sakai
April 1970,
Nature,
M Tomita, and
N Suzuki, and
Y Matsumoto, and
K Hirano, and
N Umeda, and
K Sakai
November 1988,
Mutation research,
M Tomita, and
N Suzuki, and
Y Matsumoto, and
K Hirano, and
N Umeda, and
K Sakai
June 1986,
International journal of radiation biology and related studies in physics, chemistry, and medicine,
M Tomita, and
N Suzuki, and
Y Matsumoto, and
K Hirano, and
N Umeda, and
K Sakai
February 1984,
Gan,
M Tomita, and
N Suzuki, and
Y Matsumoto, and
K Hirano, and
N Umeda, and
K Sakai
October 1988,
International journal of radiation biology,
M Tomita, and
N Suzuki, and
Y Matsumoto, and
K Hirano, and
N Umeda, and
K Sakai
November 1966,
Radiation research,
M Tomita, and
N Suzuki, and
Y Matsumoto, and
K Hirano, and
N Umeda, and
K Sakai
November 1989,
Chemical & pharmaceutical bulletin,
M Tomita, and
N Suzuki, and
Y Matsumoto, and
K Hirano, and
N Umeda, and
K Sakai
May 1983,
Radiation research,
