Hypoxic cell sensitizers and heavy charged-particle radiations.

Stationary-phase populations of Chinese hamster V-79 cells were irradiated with 250 kV X-rays and the Bragg peaks (spread to a width of 4 cm) of energetic He-, C-, Ne-, and A-ion beams produced at the 184-inch cyclotron and BEVALAC at Lawrence Berkeley Laboratory. Survival curves were generated with each radiation for cells suspended in air-saturated and nitrogen-saturated medium with and without sensitizer present. The oxygen enhancement ratios (OERs) measured for X-rays with 1mM metronidazole and 0.5 mM misonidazole were 2.0 and 1.6 respectively. The OERs without sensitizer for He-, C-, Ne-, and A-ion Bragg peaks were 2.4, 1.7, 1.6 and 1.4 respectively. For each type of radiation tested the presence of hypoxic-cell sensitizers resulted in an additional reduction in the measured OERs, indicating that these drugs should be of benefit in the radiotherapy planned with these and other high LET radiations.