Cell biology of hyperthermia and radiation

Hyperthermia may have important implication for cancer therapy because heat has selective effect on radioresistant cells, that is, S phase cells and hypoxic tumor cells which may be heat sensitive because of their low pH or pool nutrition. In the case of heat alone, the curves of logarithmic survival vs. duration of heating resemble X-ray survival curves with the exception that thermal tolerance develops after 3 - 4 hr of heating. Thermal tolerance is observed also both in vivo and in vitro when 2nd heat treatment follows first treatment after 10 - 24 hr incubation at 37 deg C. There is considerable evidence from the use of membrane active agents and local anesthetics that the target for heat killing involves damage to plasma membranes. Heat combined with X-ray irradiation reduces both the D0 and the shoulder of X-ray survival curves. S phase cells are selectively radiosensitized by hyperthermia, and the difference in radiosensitivity during the cell cycle is reduced or eliminated by hyperthermia. The sequence of heat and irradiation is quite important in determining the amount of lethality, and the greatest effect is observed when X-ray irradiation is applied during heating intervals. When heating follows irradiation after 2 - 3 hr, thermal enhancement is greater in tumors or the cells at low pH than skins or the cells at normal pH. Damage to the target for heat radiosensitization results in the increase in radiation-induced chromosomal aberration. (Yamashita, S.)