Effect of anoxic radiosensitizers on cellular and mitochondrial oxygen consumption and respiration control ratio.
Misonidazole increased oxygen consumption of Ehrlich ascites cells and reversed the blockage of oxidative phosphorylation induced by amytal and KCN. It alos increased oxygen consumption of mitochondria in the presence of alpha-ketoglutarate substrate, but decreased the respiratory control ratio. Cellular oxygen consumption decreased, but mitochondrial consumption was increased by metronidazole, and the respiratory control ratio was not affected by this substance. It was concluded that misonidazole influences respiration in a similar way to uncouplers, and the interaction site for both substances is at the NADH level. These respiratory effects can be of importance in altering radiation response in multicellular tissues.
D000654:Amobarbital / Q000494:pharmacology; D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism; D003486:Cyanides / Q000494:pharmacology; D066298:In Vitro Techniques; D007656:Ketoglutaric Acids / Q000378:metabolism; D008795:Metronidazole / Q000494:pharmacology*; D008930:Mitochondria, Liver / Q000378:metabolism; D009593:Nitroimidazoles / Q000494:pharmacology*; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*
D003486:Cyanides; D007656:Ketoglutaric Acids; D009593:Nitroimidazoles; D011838:Radiation-Sensitizing Agents; D008795:Metronidazole; D000654:Amobarbital