Effects of sensitizers on cell respiration: II. The effects of hypoxic cell sensitizers on oxygen utilization in cellular and chemical models.
The metabolic activity of nitroheterocyclic sensitizers could limit their usefulness in vivo. Biochemical mechanisms of drug metabolism, toxicity and effects on cell respiration have been studied in microsomes, and the kinetics of the simulated redox reactions determined by pulse radiolysis. Stimulated oxidation of coenzyme, glucose, ascorbate or glutathione substrate radicals by nitroheterocyclic sensitizers, with the concomitant appearance of the respective nitro radical anions, is observed. Under hypoxia, the nitro radical anions decay slowly by second order processes, forming reduced metabolites. In air, the nitro radical anions react with oxygen forming superoxide radical anions, peroxide and regenerating the drug. Nitro radical-anions also react with cytochrome-c indicating a possible interference with mitochondrial energy metabolism.
D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism; D006571:Heterocyclic Compounds / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D051379:Mice; D008861:Microsomes / Q000378:metabolism; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000187:drug effects*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*
D006571:Heterocyclic Compounds; D011838:Radiation-Sensitizing Agents