Evidence suggesting that the mechanism for aerobic and hypoxic cytotoxicity of nitroheterocycles is the same.
The fluorescence of three nitroheterocycles (AF-2, trans-5-amino-3-(2-(5-nitro-2furyl) vinyl)-1,2,4-oxadiazole and 4-NQO) was used to quantitate cellular uptake and binding using a fluorescence-activated cell sorter. Mean cellular fluorescence, proportional to the amount of bound drug, allowed accurate prediction of the amount of cell killing. At equitoxic concentrations, the same amount of drug was bound under either aerobic or hypoxic conditions. In addition, 5 mM glutathione was equally effective at inhibiting aerobic and hypoxic cell killing by AF-2. These results suggest that the mechanism for cell killing may be similar under aerobic and hypoxic conditions, and the presence of oxygen may influence the rate of drug uptake rather than the nature of the toxic species. The nitro anion radical, formed in the presence and absence of oxygen, seems a likely candidate for the "toxic species."
D000332:Aerobiosis; D000818:Animals; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D005453:Fluorescence; D000860:Hypoxia / Q000503:physiopathology; D007739:L Cells; D051379:Mice; D009574:Nitro Compounds / Q000494:pharmacology*; D013438:Sulfhydryl Compounds / Q000494:pharmacology; D013997:Time Factors
D009574:Nitro Compounds; D013438:Sulfhydryl Compounds