Variation of the Radiosensitizing Efficiency of RSU-1069 with Pre-irradiation Contact Times: A Rapid Mix Study

Summary

Using a cellular fast-mixing technique, the time course of radiation sensitization of hypoxic, V79 cells by various concentrations of RSU-1069 (0·25–2·5 mmol dm⁻³) and misonidazole (2·5–50 mmol dm⁻³) have been studied to distinguish between fast chemical processes and the much slower biochemical responses to ionizing radiation and the monofunctional alkylating action of RSU-1069. Under conditions of equi-concentration, misonidazole and RSU-1069 show similar radiosensitizing efficiencies for pre-irradiation contact times up to 1 s. The values of the sensitizer enhancement ratio of ∼ 1·5 for both 2-nitroimidazoles (2·5 mmol dm⁻³) is considerably less than that of 1·9–2·8 determined with misonidazole for a pre-irradiation contact time of 1 h under hypoxia. It is proposed that the enhanced radiosensitizing efficiency of RSU-1069 compared to that of misonidazole after long contact times involves, in part, the formation of ‘sub-toxic’ damage probably involving monofunctional and/or bifunctional action of RSU-1069 prior to irradiation.