Effect of simultaneous pulsed hyperthermia and pulsed radiation treatment on survival of SiHa cells

Abstract

Relatively mild temperatures (40–41.5°C) can sensitize human cells to radiation without the development of thermal tolerance to radiosensitization. Therefore there may be a therapeutic benefit to adding mild hyperthermia to brachytherapy regimens for the treatment of cancer. However, the required heating times are long (∼48 h) which renders this approach somewhat impractical. A novel alternative is to combine pulsed brachytherapy with pulsed hyperthermia to enable the total radiation dose to be given at an elevated temperature while the total heating time is kept short. A treatment schedule in which 1 Gy radiation pulses were given once per hour during 5-min heating pulses also delivered once per hour, was investigated in vitro in the human cervical carcinoma line, SiHa. The degree of cytotoxicity and thermoradiosensitization of the cells were assessed by cell survival using the colony forming assay. Cells were exposed to pulsed hyperthermia alone (5 min at 45°C, delivered once per hour), acute hyperthermia alone (45°C), pulsed radiation alone (1 Gy per hour), acute radiation alone, and simultaneous pulsed hyperthermia and pulsed radiation. Pulsed heating alone caused little cytotoxicity. However when pulsed heating was added to pulsed radiation, the level of cytotoxicity was greater than for pulsed radiation alone or acute radiation alone. The effect was also greater than would be predicted from a simple additive effect of pulsed radiation and pulsed heating. In conclusion, pulsed heating at 45°C sensitized cells to pulsed radiation without the development of thermal tolerance.

Key Words:

• Pulsed hyperthermia
• pulsed radiation
• radiosensitization