To overcome the radioresistance of hypoxic cells in solid
tumor, numerous types of radiosensitizers specifically against them have been developed. Glycididazole has a chemical structure in which two
metronidazole forms are combined, and is widely used as a hypoxic radiosensitizer in China. However, a detailed investigation of its radiosensitizing properties has not been performed. The present study reported a comparative assessment of glycididazole and
doranidazole, another hypoxic radiosensitizer. All experiments were performed using the murine
squamous cell carcinoma cell line SCCVII. Prior to X-irradiation, the cells were treated with the test drugs at concentrations of 10 mM and 200 mg/kg in vitro and in vivo, respectively. Uptake and their intratumor chemical forms were analyzed by high performance liquid chromatography (HPLC). Both drugs enhanced the reproductive cell death induced by X-irradiation under
hypoxia. However, the growth delay assay of the transplanted
tumor revealed the combination of X-irradiation and glycididazole showed a similar antitumor effect to that of X-irradiation alone, whereas
doranidazole significantly sensitized the cells to X-irradiation. HPLC analysis revealed that incorporated glycididazole was decomposed to
metronidazole and was therefore present at a lower concentration compared with that of
doranidazole. The decomposition of glycididazole to
metronidazole reduced its radiosensitizing efficiency in vivo. Elucidation of the kinetics of drugs containing metabolizable chemical forms is necessary for the optimization of clinical treatment.