Nitrofurans as radiosensitizers of hypoxic mammalian cells.

Our studies showed that various nitrofuran derivatives have excellent radiosensitizing properties in hypoxic Chinese hamster cells at concentrations at which there is no effect on plating efficiency. The radiosensitizing effect is primarily a dose-modifying effect, with nitrofurantoin, nitrofurazone, and nifuroxime (each at 500 ¿M) in complete medium giving enhancement ratios of 1.65, 2.0, and 2.2, respectively. In parallel studies, the radiosensitizing effect of molecular oxygen (air-saturated conditions) was found to be dose modifying, with an enhancement ratio of ~2.9. Selective radiosensitization in hypoxia has been demonstrated in proliferating populations of cells in every phase of the cell cycle, as well as in nonproliferating populations which were contact inhibited at the time of irradiation. In all cell populations tested, these compounds did not alter radiosensitivity in air-saturated conditions. The permeability of phospholipid membranes to nitrofurazone in 0.1 M NaCl has been measured, and a permeability constant (K) of 1.5 (±0.7) X IO"5 cm/sec