Cellular effects of hyperthermia: relevance to the minimum dose for thermal damage.

The specific mechanism of cell killing by hyperthermia is unknown, but the high activation energy of cell killing and other responses to hyperthermia suggest that protein denaturation is the rate-limiting step. Protein denaturation can be directly monitored by differential scanning calorimetry and in general there is a good correlation between protein denaturation and cellular response. Approximately 5% denaturation is necessary for detectable killing. Protein denaturation leads to the aggregation of both denatured and native protein with multiple effects on cellular function.