Hyperthermia is generally used in combination with chemo and radiation therapy in the treatment of various cancers. Thus far, most studies have focused on the additive effects of heat shock. However, it is also critical to understand the solitary effect of heat shock stress on mammalian cells. DNA double-strand breaks (DSBs) are known to be generated by ionizing radiation and a variety of DNA modifying reagents. As shown by neutral comet assays and γH2AX (phosphorylated histone H2AX at serine 139) focus formation, heat shock also induces DSBs. While existing literature suggests that heat shock leads to cell death through the induction of DSBs, the pathway involved in repairing heat-induced damage remains to be elucidated. In the current review, we examined the history of hyperthermia, from the discovery of DSBs after heat shock, to our recent finding regarding the homologous recombination repair pathway after heat shock.

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