Stratford I J
Br J Cancer. 1978 Jul;38(1):130-6. doi: 10.1038/bjc.1978.172.
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.
已测定灭滴灵(1-(2-硝基咪唑-1-基)-3-甲氧基-2-丙醇)在体外对哺乳动物细胞的毒性与氧张力的关系。灭滴灵在缺氧条件下(氧含量低于10/10⁶)毒性最大。分次给药实验表明,致死性损伤可被氧“修复”,这种修复的程度与时间有关,且是氧浓度的函数,在37℃下暴露于空气中2小时后修复作用最大。与辐射损伤不同,在分次给药间隔期间,适度的热疗(41℃)不会抑制这种修复。讨论了这些结果对于灭滴灵在厌氧条件下毒性机制的意义。