Radiosensitization of Mouse L Cells by an Electron Affinic Radiosensitizer,R0-07-0582 under an Extremely Hypoxic Condition

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The present investigation was undertaken with the hope for elucidating the effect of a radiosensitizer on mouse L cells in culture following X-irradiation. Under the aerobic condition, a survival curve of irradiated cells showed a shoulder region with the extrapolation number of 6.4 and mean lethal dose (D_0 value) of 126 rad. On the other hand, under the extremely hypoxic condition prepared with nitrogen gas using a stainless steel apparatus, a survival curve was found to show no shoulder region, having extrapolation number of 1.1 and D_0 Value of 629 rad. Thus, the oxygen enhancement ratio (o.e.r.) was calculated as a factor 5. An electron affinic radiosensitizer, Ro-07-0582 revealed a pronounced sensitizing effect under the extremely hypoxic condition by an enhancement ratio 3.9 at a concentration of 10 mM. The sensitizer reduced D_0 Value with increasing concentration of the drug. The evidence obtained suggests that Ro-07-0582 acts as oxygen-mimic, although the drug shows no radiosensitizing effect at low concentration and low irradiation doses. It has been suggested that the radioresistant hypoxic cells cause a serious problem to the radiotherapy of certain human tumors. Radiosensitization with electron affinic compounds was proposed by Adams and Dewey. Recently, Asquith et al. have reported that 2-nitroimidazole, Ro-07-0582, is the most effective electron affinic radiosensitizer.