| Abstract: |
This chapter focuses on chemical modifiers reviews the present state of the art. Agents that potentiate hyperthermic cytotoxicity by lowering temperature threshold include local anesthetics, short chain aliphatic alcohols, energy depleters, and lactate transport inhibitors. The major hyperthermic sensitization is usually obtained with inhibitors of oxidative phosphorylation only in the absence of glucose in the media, indicating that lowering the cellular energy level to the critical level renders cells extremely heat sensitive. In pursuing the cellular mechanisms of heat-induced cytotoxicity, early cell culture studies suggested that cancer cells were more sensitive to heat than were normal cells. Hyperthermic sensitizer can be defined as any compound that is not cytotoxic at 37 °C but at elevated temperatures becomes cytotoxic. So characterized, this would exclude most of the chemotherapeutic agents from the present discussion, since they are by themselves cytotoxic at 37 °C, but when combined with heat, further enhance cellular injury. © 1988 by Taylor & Francis Group, LLC. |
