Hyperthermia radiosensitization in human glioma cells comparison of recovery of polymerase activity, survival, and potentially lethal damage repair.

Abstract

DNA polymerase inactivation is compared to thermal radiosensitization and inhibition of damage recovery in human glioma cells. Two human glioma cell lines (U87MG and U373MG) were exposed to hyperthermia and irradiation. Hyperthermia was given at 43 degrees C and 45 degrees C and DNA polymerase alpha + delta + epsilon and beta activities were measured. Hyperthermia was given at various times before irradiation and the degree of radiosensitization and polymerase activity was assessed at various times after heating. In addition the ability of cells to undergo repair of potentially lethal radiation damage was assessed for cells irradiated at various times after heating. Polymerase alpha + delta + epsilon and polymerase beta both recovered after heating but polymerase beta was faster and was complete in U373MG but not in the U87MG cell lines after 48 h incubation after heating (45 degrees C, 60 min). Incubation, between hyperthermia and irradiation resulted in a loss of radiosensitization and a loss of inhibition of repair of potentially lethal damage. These changes correlated well with recovery of polymerase beta but not with polymerase alpha + delta + epsilon. The correlation of polymerase beta activity and thermoradiosensitization and its recovery indicate that polymerase beta may be one of the mechanisms involved in thermoradiosensitization.