Oxygen dependence for chemosensitization by misonidazole

Misonidazole (MISO) potentiates the cell killing effect of certain chemotherapy agents, but only under hypoxic conditions. The purpose of the present study was to define the range of oxygen concentrations over which chemosensitization by MISO takes place using mammalian cells cultured in vitro, and to compare this with the oxygen levels required for radiosensitization. V-79 hamster cells, attached to permanox dishes, were gassed with known concentrations of oxygen (less than 10 to 200,000 ppm) and treated with 1 and 5 mM MISO for 4 h previous to exposure to the chemotherapy agent, melphalan. In a parallel series of experiments, under the same gassing conditions, cells were irradiated with graded doses of X-rays at various oxygen concentrations. The K factor i.e. the oxygen concentration which defined half the maximum effect was found to be approximately 4776 ppm for radiosensitization and approximately 400 ppm for chemosensitization by MISO. It is evident that a significantly more stringent level of hypoxia is required for chemosensitization by MISO to take place than for radiosensitization.