Thermal stress and the disruption of redox-sensitive signalling and transcription factor activation: possible role in radiosensitization.
In spite of ongoing research efforts, the specific mechanism(s) of heat-induced alterations in the cellular response to ionizing radiation (IR) remain ambiguous, in part because they likely involve multiple mechanisms and potential targets. One such group of potential targets includes a class of cytoplasmic signalling and/or nuclear transcription factors known as immediate early response genes, which have been suggested to perform cytotoxic as well as cytoprotective roles during cancer therapy. One established mechanism regulating the activity of these early response elements involves changes in cellular oxidation/reduction (redox) status. After establishing common alterations in early response genes by oxidative stress and heat exposure, one could infer that heat shock may have similarities to other forms of environmental antagonists that induce oxidative stress. In this review, recent evidence supporting a mechanistic link between heat shock and oxidative stress will be summarized. In addition, the hypothesis that one mechanism whereby heat shock alters cellular responses to anticancer agents (including hyperthermic radiosensitization) is through heat-induced disruption of redox-sensitive signalling factors will be discussed.
Gius
D
D
Molecular Radiation Oncology Section, Radiation Oncology Branch, Radiation Oncology Sciences Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. giusd@mail.nih.gov
Mattson
D
D
Bradbury
C M
CM
Smart
D K
DK
Spitz
D R
DR
D000818:Animals; D006801:Humans; D006979:Hyperthermia, Induced; D010084:Oxidation-Reduction; D011836:Radiation Tolerance / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology* / Q000528:radiation effects; D014157:Transcription Factors / Q000502:physiology*
D014157:Transcription Factors