Anderson R F, Patel K B
Radiat Res. 1983 Mar;93(3):516-24.
Prolonged preirradiation incubation of nitroaromatic radiosensitizers with Escherichia coli cells has been found to increase the degree of radiosensitization of the cells in anoxia. Studies with E. coli strains which differ in their nitroreductase activity indicate that the increase in sensitization arises from the action of metabolites produced by the nitroreductase system of the cell. The metabolites alone appear to decrease the extrapolation number of irradiated hypoxic cells and when combined with the parent compound give a biphasic survival curve. The combination of misonidazole (1 mmole dm-3) and its metabolites (1 mmole dm-3) gave initial and final enhancement ratios of 2.4 and 1.4, respectively. The final enhancement ratio is that expected for 1 mmole dm-3 misonidazole alone, whereas the initial enhancement ratio indicates that the metabolites potentiate the action of misonidazole. The preirradiation incubation effect is removed by dithiothreitol at concentrations which do not affect the radiosensitization level of the nitroaromatic sensitizer. This result indicates that the active metabolite probably depletes a certain amount of the free-thiol compounds inside the cell which assist in the repair of radiation-induced damage.
已发现将硝基芳香族放射增敏剂与大肠杆菌细胞进行预照射前长时间孵育，可增加细胞在缺氧状态下的放射增敏程度。对硝基还原酶活性不同的大肠杆菌菌株进行的研究表明，增敏作用的增强源于细胞硝基还原酶系统产生的代谢产物的作用。单独的代谢产物似乎会降低受照射缺氧细胞的外推数，并且与母体化合物结合时会产生双相存活曲线。米索硝唑（1 mmol dm⁻³）及其代谢产物（1 mmol dm⁻³）的组合分别产生了2.4和1.4的初始和最终增强比。最终增强比是单独1 mmol dm⁻³米索硝唑所预期的值，而初始增强比表明代谢产物增强了米索硝唑的作用。二硫苏糖醇在不影响硝基芳香族增敏剂放射增敏水平的浓度下可消除预照射孵育效应。这一结果表明，活性代谢产物可能消耗了细胞内一定量有助于修复辐射诱导损伤的游离硫醇化合物。
