Radiosensitization by misonidazole, pimonidazole and azomycin and intracellular uptake in human tumour cell lines

Radiosensitization of two human tumour cell lines, HT-1080 and LoVo was compared with Chinese hamster line V73-379A. Although the two human lines were more radiosensitive than V79, enhancement ratios for misonidazole, pimonidazole and azomycin were similar for all three. In all cells uptake of misonidazole and azomycin was very rapid; that of pimonidazole was initially much slower before reaching a plateau. The ratios of intracellular concentration of radiosensitizer to extracellular concentration (Ci to Ce)for misonidazole were 0.8 (HT-1080) and 0.7 (LoVo and V79); for azomycin 0.9 (HT-1080 and LoVo) and 0.8 (V79). CiCe for pimonidazole varied with cell line [1.8 (LoVo), 2.6 (HT-1080) and 3.3 (V79)]. When average cell volume was taken into consideration, concentrations of non-protein sulphydryl were very similar [4.2 (HT-1080), 5.6 (LoVo), 5.7 (V79) m mol dm-3]. MPSH levels expressed as n mol/mg protein were also similar. (author)