Radiosensitizing and cytotoxic properties of misonidazole on glutathione synthetase deficient human fibroblasts.
The cytotoxic and radiosensitizing effects of misonidazole have been studied on glutathione synthetase deficient fibroblasts and on their controls. At any concentration from 0.1 to 4 mM, deficient cells are more sensitive to the cytotoxic effect of misonidazole than the control cells. The differential effect between the two cell strain concerns both the shoulder and the slope of the survival curve, thus suggesting that NPSH play a role in the determination of misonidazole cytotoxicity. Like oxygen, misonidazole clearly sensitizes deficient cells to a lesser extent than control cells. For both cell strains, the maximum sensitizing effect of misonidazole is very close to that of oxygen (1.5 and 1.5 for deficient cells, 2.8 and 2.9 for control cells, respectively). The sensitizing effect of misonidazole appears in the same concentration range for both cell strains, with a maximal effect at lower concentrations for deficient cells.
D002470:Cell Survival / Q000187:drug effects*; D002588:Cesium Radioisotopes; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology / Q000528:radiation effects; D005720:Gamma Rays; D005978:Glutathione / Q000502:physiology; D005981:Glutathione Synthase / Q000172:deficiency*; D006801:Humans; D008920:Misonidazole / Q000494:pharmacology*; D009593:Nitroimidazoles / Q000494:pharmacology*; D010453:Peptide Synthases / Q000172:deficiency*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*
D002588:Cesium Radioisotopes; D009593:Nitroimidazoles; D011838:Radiation-Sensitizing Agents; D008920:Misonidazole; D010453:Peptide Synthases; D005981:Glutathione Synthase; D005978:Glutathione