RELATIONSHIP OF CELLULAR REDOX STATE AND THERMOTOLERANCE

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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 alteration 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 center around GSH metabolism. There is also interest in the role that GSH has on maintaining the integrity of the membrane. Heat sensitizers, such as polyamines will be studied to determine their impact on the cellular redox systems as reflected by GSH levels. The effect of hyperthermia stress on redox status is continuing to be investigated. Particularly attention is being directed to dissecting out the components of the heat stress response and oxidative stress related enzymes.