Evidence for the Involvement of Double-Strand Breaks in Heat-Induced Cell Killing
- 15 December 2004
- journal article
- Published by American Association for Cancer Research (AACR) in Cancer Research
- Vol. 64 (24), 8839-8845
- https://doi.org/10.1158/0008-5472.can-04-1876
Abstract
To identify critical events associated with heat-induced cell killing, we examined foci formation of γH2AX (histone H2AX phosphorylated at serine 139) in heat-treated cells. This assay is known to be quite sensitive and a specific indicator for the presence of double-strand breaks. We found that the number of γH2AX foci increased rapidly and reached a maximum 30 minutes after heat treatment, as well as after X-ray irradiation. When cells were heated at 41.5°C to 45.5°C, we observed a linear increase with time in the number of γH2AX foci. An inflection point at 42.5°C and the thermal activation energies above and below the inflection point were almost the same for cell killing and foci formation according to Arrhenius plot analysis. From these results, it is suggested that the number of γH2AX foci is correlated with the temperature dependence of cell killing. During periods when cells were exposed to heat, the cell cycle-dependent pattern of cell killing was the same as the cell cycle pattern of γH2AX foci formation. We also found that thermotolerance was due to a depression in the number of γH2AX foci formed after heating when the cells were pre-treated by heat. These findings suggest that cell killing might be associated with double-strand break formation via protein denaturation.Keywords
This publication has 34 references indexed in Scilit:
- Histone H2AX phosphorylation is dispensable for the initial recognition of DNA breaksNature, 2003
- DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociationNature, 2003
- Role of BRCA1 in heat shock responseOncogene, 2003
- Hyperthermic radiosensitization: mode of action and clinical relevanceInternational Journal of Radiation Biology, 2001
- Heat-induced accumulation of p53 and hsp72 is suppressed in lung fibroblasts from the SCID mouseInternational Journal of Radiation Biology, 2000
- Loss of S-phase-dependent radioresistance in irs-1 cells exposed to X-raysMutation Research/DNA Repair, 1994
- Apurinic site induction in the DNA of cells heated at hyperthermic temperaturesJournal of Cellular Physiology, 1987
- DNA Polymerase α and β Activities during the Cell Cycle and Their Role in Heat Radiosensitization in Chinese Hamster Ovary CellsRadiation Research, 1985
- Effect of Hyperthermia on CHO DNA Polymerases α and βRadiation Research, 1982
- Variation in Sensitivity to Heat Shock during the Cell-cycle of Chinese Hamster Cellsin VitroInternational Journal of Radiation Biology and Related Studies in Physics, Chemistry and Medicine, 1971