The heat-induced gamma-H2AX response does not play a role in hyperthermic cell killing.
OBJECTIVE
The goal of this study was to determine whether the heat-induced formation of gamma-H2AX foci is involved in hyperthermic cell killing.


METHODS
The heat-induced gamma-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 gamma-H2AX response in thermotolerant cells. The initial magnitude of the gamma-H2AX response was found to be the same in all cell lines with altered heat sensitivity. Furthermore, no differences in the resolution of gamma-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 gamma-H2AX response does not play a role in heat-induced cell killing, thereby adding further evidence that the heat-induced gamma-H2AX foci are not due to DNA double strand breaks.
Division of Radiation and Cancer Biology, Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO, USA. alaszlo@radonc.wustl.edu
Andrei
A
Laszlo
Ilona
I
Fleischer
D000818:Animals; D018053:Arsenites / Q000494:pharmacology; D001383:Azetidinecarboxylic Acid / Q000494:pharmacology; D016466:CHO Cells; D002172:Canavanine / Q000494:pharmacology; D002460:Cell Line; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D005990:Glycerol / Q000494:pharmacology; D055551:HSP27 Heat-Shock Proteins / Q000502:physiology; D006657:Histones / Q000502:physiology*; D006358:Hot Temperature; D006801:Humans; D018832:Molecular Chaperones / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects
D018053:Arsenites; C468783:H2AX protein, human; D055551:HSP27 Heat-Shock Proteins; D006657:Histones; D018832:Molecular Chaperones; C475961:gamma-H2AX protein, mouse; D002172:Canavanine; D001383:Azetidinecarboxylic Acid; C015001:arsenite; D005990:Glycerol