Fig. 9

Ultrastructural alterations of transformed hepatocytes in acinar zone 3 of the liver acinus, 1 and 2 weeks after hydrodynamic tail vein injection of Akt-TAZ plasmids. (A, B) Liver acinus 1 week post-injection with a portal tract (PT) and altered hepatocytes (arrows) located in acinus zone 3. Hepatocytes near the central venule (CV) are often enlarged and vacuolated. Beneath these hepatocytes, single atypical, sometimes binucleated atypical hepatocytes (marked box and magnification in B) reveal irregular cell borders, enlarged nuclei, and several nucleoli. They are surrounded by unaltered hepatocytes with round, oval nuclei, and regular cell shapes. (C) Note massive glycogen (G) storage with tightly packed α-particles in the cytoplasm and membrane-enclosed autophagic vacuoles (arrowhead). (D) Two weeks after injection, some altered hepatocytes reveal noticeable loss of glycogen (arrows), whereas glycogen storing cells are still common (arrowhead). At the ultrastructural level (E, F), transformed hepatocytes (TH) reveal irregularly shaped nuclei and now absent glycogen storage in contrast to normal neighboring hepatocytes (HEP). Nevertheless, cell junctions and bile canaliculi are preserved (boxed magnified areas), implying their hepatocellular nature. A, B, D Stainings according to Richardson, C, E, F staining with uranyl acetate and lead citrate. Length of the lower edge A 500μm, B 80μm, C 10μm, D 111μm, E 18μm, F 10μm.