Studies on the toxicity and radiosensitizing ability of misonidazole under conditions of prolonged incubation.
Studies on the toxicity and radiosensitizing ability of misonidazole under conditions of prolonged incubation.
复制标题
米索硝唑在长时间孵育条件下的毒性和放射增敏能力的研究。
作者：
T. Wong;G. Whitmore;S. Gulyás
对CHO细胞的体外研究表明，2-硝基咪唑（米索硝唑）在缺氧条件下的毒性明显高于有氧条件下。此外，在照射前低氧条件下使用延长暴露于药物确定的存活曲线显示外推数（n）以及平均致死剂量（D 0）减少。用放射性米索硝唑进行的研究表明，在37°C下，与需氧细胞相比，乏氧细胞内放射性物质逐渐积累，并且在5小时的孵育期内，观察到乏氧细胞的摄取增加2至3倍。色谱分析表明，这种摄取的增加是由于米索硝唑代谢产物的积累。有人建议，无论是增加毒性和减少n作为一个结果，延长孵育与米索硝唑在缺氧条件下，这些代谢产物的形成有关。
In vitro studies with CHO cells indicate that the 2-nitroimidazole, misonidazole, is markedly more toxic under hypoxic conditions than under aerobic conditions. Also, survival curves determined using prolonged exposure to the drug under hypoxic conditions before irradiation have shown a reduction in the extrapolation number (n) as well as the mean lethal dose (D0). Studies with radioactive misonidazole have indicated that at 37°C there is a gradual accumulation of radioactive material within hypoxic as compared to aerobic cells and that over an incubation period of 5 hr, a 2- to 3-fold increase in uptake by hypoxic cells is observed. Chromatographic analysis has shown that this increase in uptake is due to the accumulation of metabolites of misonidazole. It is suggested that both the increase in toxicity and reduction in n as a result of prolonged incubation with misonidazole under hypoxic conditions are related to the formation of these metabolites.