Hyperthermia is currently being evaluated as a potential cancer treatment modality. The mechanism(s) of hyperthermia killing and the induction of thermal resistance (thermotolerance) are not known. We will examine the role of the cellular reduction potential during and after heating to determine its role or alternation during thermal stress. This will be accomplished by using drugs which either bind GSH or prevent its synthesis. There appears to be a relationship between the synthesis of heat shock proteins and the induction of heat resistance. The effect of thiol modulation will be studied in the context of heat shock proteins. Recently, several compounds have been introduced which elevate cellular GSH. These compounds will be synthesized and evaluated in regard to thermal response. Continued effort to inter-relate oxidative stress and the biochemical induction of genetic materials ceter around GSH metabolism. There is also interest in the role that GSH has on maintaining the integrity of the membrane. Moreover, the role membrane damage and how this damage modifies intracellular GSH with subsequent genetic expression of heat shock proteins is being utilized to study possible explanations for cellular heat and drug resistance.
NIH ExPorter
NIH ExPorter