CELL-KILLING, DNA-POLYMERASE INACTIVATION AND RADIOSENSITIZATION TO LOW-DOSE RATE IRRADIATION BY MILD HYPERTHERMIA IN 4 HUMAN CELL-LINES

Four human cell lines (one fibroblast, two melanoma and one glioma) we re evaluated for their responses to hyperthermia and thermalradiosensi tization. For mild hyperthermia (40-42 degrees C), there was little to no chronic thermotolerance development during protracted heating for up to 72 h. In addition, there was no significant thermotolerance for polymerase inactivation during mild hyperthermia. For high temperature hyperthermia, polymerase beta was more thermal sensitive than aphidic olin sensitive polymerase alpha + delta + epsilon, (termed polymerase alpha) but during mild hyperthermia the relative sensitivities were re versed. Polymerase beta was resistant to mild hyperthermia and polymer ase alpha was very sensitive. Within each cell line there was a correl ation between polymerase alpha inactivation and the degree of radiosen sitization (TER) and amongst the cell lines the most radiation resista nt cell line had less polymerase alpha inactivation than the most sens itive cell line for similar values of TER's. These data indicate that, amongst the cell lines, radiosensitivity and polymerase alpha sensiti vity may influence TER and that for a given cell line, or possibly tum our, polymerase alpha inactivation may have potential as an indicator to determine TER for mild hyperthermia treatments in radiosensitizatio n to low dose rates.