Comparison of survival and DNA double strand breaks for mild hyperthermia and low dose rate/pulsed low dose rate irradiation in human cells.

Long duration mild hyperthermia (LDMH) has been shown to be an effective radiosensitizer when combined with low dose rate irradiation and pulsed low dose rate irradiation. These protocols are being investigated to determine if these effects can be related to DNA double strand breakage (dsb). In our studies we used human melanoma (SK mel-3) and fibroblasts (AG1522). A low dose rate was given at 0.88 cGy/min while pulsed doses were given at 150 cGy/min. Our results showed that the degree of thermal radiosensitization (TER) increased as the average dose rate decreased. This was seen for both the survival endpoints and the degree of DNA strand breaks. There was a very good correlation between the TER and the degree of DNA strand breaks.In conclusion our data show that LDMH is an effective radiosensitizer for both LDR and PSLDR and this may also be an effective clinical protocol. The quantity of DNA dsb's appears to be related to TER and may be predictive of the degree of radiosensitization.