Stimulatory, permeabilizing, and toxic effects of amphotericin B on L cells.
High concentrations of amphotericin B (AmB) killed mouse L cells, but low concentrations increased plating efficiency and stimulated the incorporation of labeled precursors into DNA and RNA. Thus, there were two disparate effects of AmB on L cells, stimulatory and toxic, and they occurred in distinct dose-related stages. AmB also affected the permeability of L cells. In dose-response studies, increases in cell membrane permeability, measured as the loss of K+ ions, occurred along with the stimulation of [3H]uridine incorporation into RNA. In contrast, stimulation of [3H]thymidine incorporation into DNA was only observed in cells recuperating from AmB-induced permeability changes. When the K+ concentration in the medium was lowered to 0.5 from 4.5 mM, or when 1 mM ouabain was added to the cultures, cell killing was potentiated, but the stimulatory and permeabilizing effects of subtoxic concentrations of AmB were unaffected. Furthermore, etruscomycin, a polyene antibiotic without any permeabilizing effects, nevertheless induced an enhancement of plating efficiency and of incorporation of [3H]uridine into RNA and [3H]thymidine into DNA. Our results suggest that the dose-related stimulatory, permeabilizing, and toxic effects of AmB most probably have distinct mechanisms of action and may be independent of one another.
D000666:Amphotericin B / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D001345:Autoradiography; D002455:Cell Division / Q000187:drug effects; D002463:Cell Membrane Permeability / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D003470:Culture Media; D007739:L Cells / Q000187:drug effects*; D008155:Lucensomycin / Q000494:pharmacology; D051379:Mice; D010042:Ouabain / Q000494:pharmacology; D011188:Potassium / Q000502:physiology; D012313:RNA / Q000096:biosynthesis; D013936:Thymidine / Q000378:metabolism; D014529:Uridine / Q000378:metabolism
D003470:Culture Media; D008155:Lucensomycin; D010042:Ouabain; D012313:RNA; D000666:Amphotericin B; D011188:Potassium; D013936:Thymidine; D014529:Uridine