Thermal enhancement of cellular radiation damage: a review of complementary and synergistic effects.

Hyperthermia treatment can kill mammalian cells in a time and temperature dependent manner. Thermal sensitivity varies extensively among various cell lines in culture and cellular molecular and ultrastructural studies have not resolved which cellular mechanisms underlie thermal cell killing and radiosensitization. The response of cells to heat and radiation are complementary under certain conditions found in human tumors, such as hypoxia, low pH, low nutrient and the S-phase of the cell cycle. Thus, hyperthermia can be used as a complementary treatment modality in the radiotherapy of human cancer. Further studies show that heat treatment causes radiosensitization which is in part associated with the inhibition of repair of radiation damage and is strongly dependent on temperature and on the sequencing. In addition, the conditions such as pH and oxygenation during treatment sequencing can influence the degree of recovery of cells. These factors may be exploited in optimizing therapeutic gain in clinical cancer therapy. Data are shown that transformation from the normal to the tumorigenic state causes random small changes in radiosensitivity and heat sensitivity. Also, treatments combining heat and radiation can lead to increased or decreased transformation in cells depending on the treatment sequence.