Detection of primary antimitochondrial activity of drugs in cultured mammalian cells utilizing glutamine as the carbon source.
Growth of guinea-pig keratocytes (GPK) proceeded normally in standard medium in which glutamine (mitochondrial substrate) replaced glucose as the carbon and energy source. Cells in the glucose-free glutamine cultures were much more sensitive to the toxic and growth-inhibiting effects of the antimitochondrial drugs ethidium bromide, chloramphenicol and oligomycin than cells in glucose-containing cultures. In the latter, cells continued to proliferate in the presence of these drugs after 2-3 days incubation, but in the non-fermenting cells growth was arrested within 24 h and there was more than 95% cell death after 2 days. Cycloheximide, a general inhibitor of protein synthesis in eukaryotic cells, showed no selective inhibition of growth and glutamine and glucose cultures were equally affected. The system appears to be useful for the detection of primary antimitochondrial activity of drugs in general.
D000818:Animals; D002478:Cells, Cultured; D002701:Chloramphenicol / Q000494:pharmacology*; D003315:Cornea / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D003513:Cycloheximide / Q000494:pharmacology*; D004996:Ethidium / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism*; D006168:Guinea Pigs; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009840:Oligomycins / Q000494:pharmacology*
D009840:Oligomycins; D005973:Glutamine; D002701:Chloramphenicol; D003513:Cycloheximide; D004996:Ethidium; D005947:Glucose