Variation of the radiosensitizing efficiency of RSU-1069 with pre-irradiation contact times: a rapid mix study.

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 approximately 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.