EFFECT OF LYSOSOME MODIFICATION ON THE HEAT POTENTIATION OF RADIATION-DAMAGE AND DIRECT HEAT DEATH OF BP-8 SARCOMA-CELLS

It has been suggested that lysosomes represent the intracellular target responsible for heat potentiation of radiation damage and direct heat death in mammalian cells. To investigate the hypothesis that heat damages cells by lysosmal activation, BP-8 murine sarcoma celle were treated with trypan blue. This agent accumulates within lysosomes and causes pronounced inhibition of lysosmal enzymes. To evaluate the possibility that heat damage is mediated by lysosmal membrane instability and leakage of hydrolases into the cytoplasm, BP-8 cells were treated with a membrane labilizer (retinol) or stabilizer (hydrocortisone). The pre-treated cells were then subjected to hyperthermia (1 hr incubation at 37°-43°C), or to X-irradiation at normal (37°C) vs elevated (41.5°C) temperatures. The results indicate that pretreatment with trypan blue, retinol or hydrocortisone does not exert any effect on the heat response of BP-8 sarcoma cells. Therefore, it would seem unlikely that lysosomes are responsible for either thermal enhancement of radiation damage or direct heat-induced cell death. © 1979.