Abstract
[Purpose] Aim of the present study was to clarify the hypoxic radiosensitizing effects of novel 2-nitoroimidazole acetamide (2NIA) derivatives on human lung cancer cells.
[Materials and Methods] Human lung carcinoma A549 cells grown in exponential phase in alpha-MEM supplemented with 10% FBS were used throughout the experiments. The cells were trypsinized, suspended in complete medium which was supplemented with the sensitizers (1mM). The suspensions of 0.5 ml in a glass tube were flushed with humidified mixed gas (95%air+5% CO2 or 95%N2+5%CO2) at room temperature. The cells were irradiated with 6MV X-rays. Cell survival was obtained from the colony formation assay. The 2NIA derivatives (TX-2243, TX-2244, TX-2246) and etanidazole were used as the sensitizers.
[Results and Discussions] Oxygen enhancement ratio of hypoxic cells exposed to X-rays without the sensitizer was 2.78 based on 10% survival dose (D10). Enhancement ratio (ER=(D10 c/o sensitizer) / (D10 c/ sensitizer)) in the presence of TX-2243, TX-2244, TX-2246 and etanidazole was 1.13, 1.50, 1.56 and 1.75, respectively. On the other hand, ER based on 50% survival dose (D50) was 1.50 for TX-2243, 1.54 for TX-2244, 1.59 for TX-2246 and 1.69 for etanidazole. ERs for TX-2244 and TX-2246 were small as compared with that of etanidazole, but was significant. Present study suggested that both TX-2244 and TX-2246 were useful as the hypoxic cell radiosensitizer for human lung cancer cells. Characteristics of radiosensitizing effect of TX2243 was unusual. For TX-2243, although the small radio sensitizing effect (ER=1.13) at D10 was observed, the large effect (ER=1.50) at D50 was mentioned. The mechanisms of hypoxic radiosensitization of 2NIA derivatives still remain to be investigated.
