Radiosensitizing and toxic effects on the 2-nitroimidazole Ro-07-0582 in hypoxic mammation cells.
Radiosensitizing and toxic effects on the 2-nitroimidazole Ro-07-0582 in hypoxic mammation cells.
复制标题
2-硝基咪唑 Ro-07-0582 在缺氧乳腺细胞中的放射增敏和毒性作用。
作者：
B. Moore;B. Palcic;L. Skarsgard
已在两种中国仓鼠细胞系CHO和CH 2B/sub 2/中对亲电子2-硝基咪唑Ro-07-0582的特性进行了体外检查。该药物被发现以高效率选择性地使缺氧细胞对辐射损伤敏感。在浓度大于10 mM时，药物在缺氧培养物中的剂量调整因子约为3.0。它不会改变需氧细胞的反应。用Ro-07-0582对细胞进行辐射前或辐射后处理几乎没有影响。在高细胞浓度下，许多敏化剂无效，这种化合物保留了其大部分放射增敏能力。Ro-07-0582也显示出具有化学治疗潜力，因为它在暴露几小时后对缺氧细胞显示出非常选择性的毒性。它对需氧细胞的毒性要小得多。这种性质虽然可以作为药物放射增敏作用的有用补充，但表明在Ro-07-0582的临床应用中必须小心，以避免对体内正常缺氧组织的可能损伤。
The properties of the electron-affinic 2-nitroimidazole Ro-07-0582 have been examined in vitro in two Chinese hamster cell lines, CHO and CH2B/sub 2/. The drug was found to sensitize hypoxic cells to radiation damage selectively with a high efficiency. At concentrations greater than 10 mM the drug has a dose-modifying factor of approximately 3.0 in hypoxic cultures. It does not alter the response of aerobic cells. Pre- or postirradiation treatment of cells with Ro-07-0582 has little, if any, effect. At high cell concentrations, where many sensitizers are ineffective, this compound retains most of its radiosensitizing capability. Ro-07-0582 is also shown to have a chemotherapeutic potential in that it demonstrates a very selective toxicity for hypoxic cells after a few hours of exposure. It is much less toxic to aerobic cells. This property, while it may serve as a useful complement to the radiosensitizing effect of the drug, suggests that care must be exercized in the clinical application of Ro-07-0582 to avoid possible injury to normal hypoxic tissues in the body.