CYTOTOXIC ENHANCEMENT OF LOW DOSE-RATE IRRADIATION IN HUMAN LUNG-CANCER CELLS BY MILD HYPERTHERMIA

Purpose: The aim of this study was to investigate the cell killing ind uced by low dose-rate irradiation (LDRI) simultaneously combined with long duration mild hyperthermia in LK87 human lung cancer cells. Cell cycle alteration due to this combined treatment was also observed Mate rials and Methods: Human lung adenocarcinoma cells, LK87, were treated with concurrent LDRI (50 cGy/hr) and mild hyperthermia (38 to 42 degr ees C). Cell survival was estimated by clonogenic assay. Flow cytometr y was performed with FACScan. The treatments were simultaneously perfo rmed for up to 48 hr (24 Gy). Results: Survival curves of mild hyperth ermia alone revealed development of chronic thermotolerance up to 48 h r, whereas LDRI plus hyperthermia caused an exponential decrease in su rvival. The LDRI cytotoxicities were enhanced by mild hyperthermia ove r a non-lethal temperature range. The Do values calculated from dose r esponse curves at 37, 38, 39, 40, 41 41.5 and 42 degrees C were 6.55, 5.25, 4.24, 3.99, 3.46, 1.83 and 0.70 Gy, respectively. Cell cycle ana lysis demonstrated a remarkable G2 and a mild G1 block for LDRI alone but only a GI block was observed for LDRI combined with 41 degrees C h yperthermia. Conclusion: The LDRI cytotoxicity was enhanced by long du ration mild temperature hyperthermia. The suppression of chronic therm otolerance was considered to be a mechanism involved in this sensitiza tion.