Skin sensitization by misonidazole: a demonstration of uniform mild hypoxia

Skin reactions on irradiated mouse feet were used to measure the radiosensitization of normal tissues by misonidazole (MISO). Fractionation schedules of 1, 2, 5 and 10 daily doses of X-rays were combined with either 100 mg/kg or 670 mg/kg MISO. When unanaesthetized mice were irradiated in air, significant sensitization was observed with both the high and low drug doses, in all fractionation schedules. There was no decrease in sensitization with fractionation, even using fractions as small as 5 Gy. This indicates that many of the cells in mouse skin may be marginally hypoxic, and that sensitization at low doses is possible. Irradiation in O2 without MISO rendered the skin more sensitive to X-rays than in air. MISO given 30 min before single doses of radiation further sensitized the skin, but for 10 fractions in O2 no MISO sensitization was detected. There was little evidence for cytotoxic killing in skin by MISO. Repair of radiation damage was slightly reduced when MISO was present, during or after irradiation.