Effect of radiation and hyperthermia on prostate tumor cells with induced thermal tolerance and the correlation with HSP70 accumulation

We have investigated the effects of ionizing radiation and hyperthermia on Dunning prostate carcinoma cells after the administration of a conditioning stress (either radiation or hyperthermia) and correlated the presence or absence of a survival advantage to the accumulation of the family of 70,000 kD heat shock proteins (HSP70). Fifty percent lethal dose (LD50) determinations of hyperthermia and radiation were determined by clonogenic cell survival. The LD50 for hyperthermia was 44°C for 1 hour, LD50 for high energy ionizing radiation was 500 rads. firmed that Dunning tumor cells preconditioned with hyperthermia (43°C for 1 hour) are resistant at 10 and 24 hours to a subsequent lethal heat stress (44°C for 1 hour). No radiation tolerance was noted at 10 or 24 hours after a conditioning heat stress of 43°C for 1 hour. We also found no thermal resistance at 10 or 24 hours after radiation conditioning (500 rads). The inducible HSP70 (HSP72) was present 8 and 12 hours after hyperthermia but had decayed by 24 hours. No increase in HSP72 accumulation occurred after radiation. These data suggest that radiation and hyperthermia injure cells in two distinct manners and may explain the observed synergy in the treatment regimens that include combination hyperthermia and radiation. Our results should be useful in creating models in the treatment of carcinoma of the prostate with combined radiation and hyperthermia therapy.