Varying responses of human cells with discrepant p53 activity to ionizing radiation and heat shock exposure.
OBJECTIVE
Both heat shock (HS) and ionizing radiation have an impact on the cell cycle and may induce cell cycle arrest or apoptosis. Mutations of the p53 gene are observed at a high frequency in human tumours and are recognized in about half of all human cancers. Sensitivity to radiation, heat and anticancer agents has been observed in p53(+/+) cells, but not in mutated or p53-deficient cells. Moreover, enhancement of radiosensitivity by HS has been observed in wild-type p53 cells but not in p53-deficient cells. The molecular mechanism of the differential cell response to HS or ionizing radiation is not yet understood.


METHODS
Differences in cellular response to radiation (200 kV X-ray, 1, 2, 5 Gy) and HS (39 degrees C, 41 degrees C and 43 degrees C for 30 min) on cell cycle progression of cultures of human p53 mutant cells were investigated by flow cytometry. In addition, the effects of stressors used on the expression of several heat shock genes (HSP27, HSP60, HSP70, HSC70, HSP75, HSP78, HSP90) were studied by reverse transcriptase-polymerase chain reaction.


CONCLUSIONS
Yet, with respect to HSP gene expression, different stressors produced similar effects. Combination of HS and radiation treatment significantly induced the transcription of the HSP70 gene above the level induced by each stressor alone. Cell cycle analysis, however, revealed striking differences in prolonged dynamics of cell division in response to each stressor. Thus, p53 status could be a useful indicator in predictive assays for hyperthermia cancer treatment in combination with radiation and/or chemotherapy.
Tokalov
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SV
OncoRay-Radiation Research in Oncology, Medical Faculty Carl Gustav Carus, University of Technology Dresden, Fetscherstrasse, Germany. sergey.tokalov@oncoray.de
Pieck
S
S
Gutzeit
H O
HO
D002453:Cell Cycle; D002455:Cell Division; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006360:Heat-Shock Proteins / Q000378:metabolism*; D018869:Heat-Shock Response; D006801:Humans; D009154:Mutation; D011839:Radiation, Ionizing; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D006360:Heat-Shock Proteins; D016159:Tumor Suppressor Protein p53