BILE ACID-INDUCED MORPHOLOGICAL-CHANGES IN HEPATOMA-CELLS WITH ELEVATED SODIUM-DEPENDENT BILE-ACID UPTAKE CAPACITY

McNtcp.24 cells are rat hepatoma cells that were made competent to tak e up conjugated bile acids actively from the culture medium, Treatment of McNtcp.24 cells with certain species of bile acids caused signific ant changes in cell structure, Incubation of McNtcp.24 cells in medium containing 100 mu M taurocholic acid induced a profound alteration of cellular morphology. Very large vesicles, visible by phase contrast m icroscopy, were the most prominent feature of bile acid-treated McNtcp .24 cells, Staining of cells with Oil red O and filipin indicated that the vesicles did not contain neutral lipids or free cholesterol, The vesicles remained in the cells after efflux of radiolabeled taurocholi c acid from bile acid loaded cells, indicating that these structures a re not intracellular stores of bile acids, Electron microscopic analys is of bile acid-treated McNtcp.24 cells confirmed that the vesicles we re localized within the cells, Taurine-conjugated bile acid species we re generally potent inducers of the morphological changes, although ta uroursode-oxycholic acid did not have a significant effect, Unconjugat ed bile acid species were ineffective or only mildly effective, Bile a cid treatment also caused profound alteration of mitochondrial structu re. Surprisingly, there was no significant effect on the ability of tr eated cells to oxidize fatty acids, The bile acid-treated cells remain ed viable and upon withdrawal of bile acids from the culture medium, t he cells returned to normal morphology by 24 h. The morphological chan ges observed after treatment of McNtcp.24 with bile acids are reminisc ent of the morphological changes observed in hepatocytes following ind uction of cholestasis.