Uptake and binding of teniposide (VM26) in Krebs II ascites cells.
With [3H] VM26 as marker, the uptake and binding of teniposide have been made in cells of Krebs II ascitic tumors. The intracellular accumulation of drug displayed a passive diffusion and a saturation kinetics with an apparent Michaelis-Menten constant of 37.54 10(-6) M and a flux of 13.4 nM/min/mg of protein. VM26 was rapidly taken and an equilibrium was established with the extracellular drug in about 30 min. The steady-state accumulation was diminished by Na+ and Ca2+ absence and VP16-213, whereas, K+ and Mg2+ have no effect. Energy dependence of the system was characterized by a Q10 of 1.75 +/- 0.2 and the uptake was reduced by ouabain and iodoacetamide, when 2-4-dinitrophenol and glucose absence were without appreciable change. The study of the efflux showed that about 87% of the uptaken drug was removed, the residual amount being probably irreversibly bound. The intracellular accumulation of the drug was associated with various cell organelles, however, only the nuclear fraction demonstrated a high affinity binding.
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002287:Carcinoma, Krebs 2 / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004492:Edetic Acid / Q000494:pharmacology; D005260:Female; D007460:Iodoacetamide / Q000494:pharmacology; D007700:Kinetics; D051379:Mice; D010042:Ouabain / Q000494:pharmacology; D011034:Podophyllotoxin / Q000031:analogs & derivatives*; D012964:Sodium / Q000494:pharmacology; D013713:Teniposide / Q000378:metabolism*
D010042:Ouabain; D013713:Teniposide; D004492:Edetic Acid; D012964:Sodium; D011034:Podophyllotoxin; D007460:Iodoacetamide