Split dose cytotoxic experiments with misonidazole.

The toxicity of misonidazole (1-(2-nitroimidazol-1-yl)-3-methoxy-2-propanol) towards mammalian cells in vitro has been determined as a function of O2 tension. Misonidazole under hypoxic conditions (less than 10 Parts/10(6) O2) shows the greatest toxicity. Split-dose experiments indicate that lethal damage can be "repaired" by O2, the magnitude of this repair being time dependent and a function of O2 concentration, with maximum repair in air seen after 2 h at 37 degree C. Unlike radiation damage this repair is not inhibited by modest hyperthermia (41 degrees C) during the split-dose interval. The implication of these results as regards the mechanism of misonidazole toxicity under anaerobic conditions is discussed.