Effect of hyperthermia on differential cytotoxicity of a hypoxic cell radiosensitizer, Ro-07-0582, on mammalian cells in vitro.
Effect of hyperthermia on differential cytotoxicity of a hypoxic cell radiosensitizer, Ro-07-0582, on mammalian cells in vitro.
复制标题
高温对缺氧细胞放射增敏剂 Ro-07-0582 对体外哺乳动物细胞的差异细胞毒性的影响。
作者：
I. Stratford;G. Adams
现在有证据表明，已用作放射增敏剂的几类硝基化合物也可用作缺氧细胞的特异性细胞毒性剂。 2-硝基咪唑，Ro-07-0582，（1-（2-硝基咪唑-1-基）-3-甲氧基-2-丙醇）是此类化合物，其作为细胞毒剂的有效性取决于药物浓度、接触时间和温度。在体外，Ro-07-0582 在 37°C 空气中的浓度高达 2 mM 时不会导致细胞活力丧失，即使接触数天也是如此。相比之下，缺氧细胞不能耐受低浓度的药物，即使接触时间只有几个小时。当温度升高到37℃以上时，存活曲线的斜率明显增加，例如，在41℃时（对于1mM Ro-07-0582，（200μng/ml），斜率相对于37℃时变化2-0倍。对于41℃空气中的细胞，与在37℃时一样，在所测试的药物浓度下不存在毒性作用。药物，在这些条件下单独的热疗没有细胞毒性作用。这些结果是根据阿累尼乌斯参数进行讨论的。
There is now evidence that several classes of nitro compounds which have been used as radiosensitizers also function as cytotoxic agents specific for hypoxic cells. The 2-nitroimidazole, Ro-07-0582, (1-(2-nitroimidazol-1-yl)-3-methoxy-2-propanol) is a compound of this type, and its effectiveness as a cytotoxic agent is dependent on drug concentration, contact time and temperature. in vitro, Ro-07-0582 in air at 37 degrees C does not cause loss of cell viability at concentrations up to 2 mM, even when in contact for several days. In contrast, hypoxic cells do not tolerate much lower concentrations of drugs, even if the contact time is only a few hours. When the temperature is raised above 37 degrees C, there is a pronounced increase in the slope of the survival curves, for example, at 41 degrees C (for 1 mM Ro-07-0582, (200 microng/ml), the slope changes by a factor of 2-0 relative to that for 37 degrees C. For cells in air at 41 degrees C, as at 37 degrees C, there is no toxic effect at the concentration of drug tested. In the absence of drug, there is no cytotoxic effect of hyperthermia alone under these conditions. These results are discussed in terms of Arrhenius parameters.