Comparative studies of hypoxic-cell radiosensitization using artificially hypoxic skin in vivo.
The survival of epidermal cells in vivo has been used to assess potential radiosensitizers. Mouse skin was made acutely hypoxic for the irradiations, to give radioprotection by a factor of 2.7-3.0. Several concentrations of each drug were used to determine whether any of them were more effective sensitizers than misonidazole. The SER at each concentration was determined from radiobiological dose-response curves. The blood concentration and toxicity of the compounds were also determined. The sensitizing efficiency, assessed in several ways, indicated that only Ro 03-8799 gave significantly greater sensitization than misonidazole, and then only when assessed by comparing the compounds on the basis of equimolar blood concentrations. If the comparison of efficiency was made in terms of LD50 the ranking order change. The need for a more clinically relevant test of peripheral neurotoxicity is stressed.
D000818:Animals; D002470:Cell Survival / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005260:Female; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008920:Misonidazole / Q000494:pharmacology; D009593:Nitroimidazoles / Q000494:pharmacology; D010100:Oxygen / Q000378:metabolism*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology* / Q000633:toxicity; D012867:Skin / Q000528:radiation effects*
D009593:Nitroimidazoles; D011838:Radiation-Sensitizing Agents; C033815:pimonidazole; D008920:Misonidazole; D010100:Oxygen