The effect of pre-treatment on sensitization by misonidazole at low radiation doses

When chemical agents are being used to modify the response of cells to ionizing radiation, as in the case of hypoxic cell radiosensitizers, the experimental conditions during and immediately preceding irradiation become very important. Earlier measurements in this laboratory of the sensitization produced by misonidazole at low radiation doses showed a marked loss of radiosensitization at decreasing dose, such that the sensitization at 3 Gy was only 30% of the sensitization observed at 30 Gy. Those experiments were carried out at 00C in order to avoid the toxic effects of misonidazole. The authors re-examined the sensitization produced by misonidazole at low radiation doses in experiments carried out at 370C and including a pre-irradiation incubation period of approximately 50 min., with drug present. The experiments were carried out with V-79 cells and a cell sorter was used to provide accurately known cell numbers for plating. Colony formation was assessed in the conventional manner. The results show that with this pre-treatment at 370C, the sensitization produced by 3 mM misonidazole at a dose of 3 Gy is approximately 50-70% of the sensitization observed at 30 Gy