Cell killing, DNA polymerase inactivation and radiosensitization to low dose rate irradiation by mild hyperthermia in four human cell lines

Abstract

Four human cell lines (one fibroblast, two melanoma and one glioma) were evaluated for their responses to hyperthermia and thermalradiosensitization. For mild hyperthermia (40–42°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 β was more thermal sensitive than aphidicolin sensitive polymerase α + δ + ε, (termed polymerase α) but during mild hyperthermia the relative sensitivities were reversed. Polymerase β was resistant to mild hyperthermia and polymerase α was very sensitive. Within each cell line there was a correlation between polymerase α inactivation and the degree of radiosensitization (TER) and amongst the cell lines the most radiation resistant cell line had less polymerase α inactivation than the most sensitive cell line for similar values of TER's. These data indicate that, amongst the cell lines, radiosensitivity and polymerase α sensitivity may influence TER and that for a given cell line, or possibly tumour, polymerase α inactivation may have potential as an indicator to determine TER for mild hyperthermia treatments in radiosensitization to low dose rates.