The heat-induced γ-H2AX response does not play a role in hyperthermic cell killing

Abstract

Purpose: The goal of this study was to determine whether the heat-induced formation of γ-H2AX foci is involved in hyperthermic cell killing.

Materials and methods: The heat-induced γ-H2AX response was determined in cells exhibiting various degrees of heat sensitivity. The panel of cells tested included cells that are transiently thermotolerant, permanently heat resistant, permanently heat sensitive, and permanently resistant to oxidative stress. Cells exposed to non-thermal environmental conditions that lead to protection from, or sensitization to, heat were also tested. The heat sensitivity of cells in which H2AX was knocked out was also ascertained.

Results: The protein synthesis independent state of thermotolerance, but not the protein synthesis dependent state of thermotolerance, was found to be involved in the attenuation of the γ-H2AX response in thermotolerant cells. The initial magnitude of the γ-H2AX response was found to be the same in all cell lines with altered heat sensitivity. Furthermore, no differences in the resolution of γ-H2AX foci were found among the cell lines tested. We also found that H2AX knock-out cells were not more heat sensitive.

Conclusions: We conclude that the heat-induced γ-H2AX response does not play a role in heat-induced cell killing, thereby adding further evidence that the heat-induced γ-H2AX foci are not due to DNA double strand breaks.

• Heat-shock
• hyperthermia
• γ-H2AX
• cell survival
• DNA damage