In vivo and in vitro mechanisms of radiation sensitization, drug synthesis and screening: can we learn it all from the high dose data?
The evidence for a decreased enhancement ratio of oxygen and an electron affinic radiosensitizer (misonidazole) at low doses is presented, and the mechanism of this effect is discussed. The factors which influence the magnitude of this effect, as well as the dose levels at which the effect will be significant, are identified. This will allow further characterization of this phenomenon in the future. An approach by which present and new hypoxic radiosensitizers could be made more effective at low doses is indicated.
D000818:Animals; D019328:Buthionine Sulfoximine; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D006224:Cricetinae; D003958:Diamide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D008298:Maleates / Q000494:pharmacology; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D008920:Misonidazole / Q000494:pharmacology; D010100:Oxygen / Q000502:physiology; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D013438:Sulfhydryl Compounds / Q000378:metabolism
D008298:Maleates; D011838:Radiation-Sensitizing Agents; D013438:Sulfhydryl Compounds; D003958:Diamide; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D008920:Misonidazole; C014476:diethyl maleate; D010100:Oxygen