Effect of polyenic antibiotics on Ehrlich ascites and Novikoff hepatoma cells.

The incorporation of thymidine in Novikoff hepatoma cells and Ehrlich ascites cells was severely and irreversibly inhibited by the polyenic antibiotics filipin and lucensomycin, known for their action on phospholipid-cholesterol membranes. No inhibition could be shown on regenerating liver cells or on acellular preparations from tumor cells. Despite the well-known site of action of these antibiotics on cell membranes, which was ascertained by 51Cr efflux, transcellular migration of glutamate-14C through neoplastic cells was not affected. The cells, however, became unable to exclude the acidic dyes used for viability tests. With the use of appropriate concentrations of the polyenes, the uptake of the dye was limited to the nucleus. This behavior was paralleled by a shift in the pH of the transition from orthochromatic to metachromatic staining of the nucleus after methanol fixation.