Stewart F A, Denekamp J, Randhawa V S
Br J Cancer. 1982 Jun;45(6):869-77. doi: 10.1038/bjc.1982.139.
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.
用受辐照小鼠足部的皮肤反应来测量米索硝唑（MISO）对正常组织的放射增敏作用。将每日1次、2次、5次和10次X射线照射的分割方案与100mg/kg或670mg/kg的MISO联合使用。当未麻醉的小鼠在空气中接受照射时，在所有分割方案中，高剂量和低剂量药物均观察到显著的增敏作用。即使使用低至5Gy的分割剂量，增敏作用也不会因分割而降低。这表明小鼠皮肤中的许多细胞可能处于轻度缺氧状态，并且低剂量时也可能产生增敏作用。在氧气环境中无MISO照射时，皮肤对X射线的敏感性比在空气中更高。单剂量辐射前30分钟给予MISO可进一步使皮肤增敏，但在氧气环境中进行10次分割照射时未检测到MISO增敏作用。几乎没有证据表明MISO对皮肤有细胞毒性杀伤作用。当MISO在照射期间或照射后存在时，辐射损伤的修复略有减少。
