Ultrastructural changes in mouse hepatocytes exposed to vinblastine sulfate with special reference to the intercellular junctions.

The effects of a single dose (0.5 mg) of the antimicrotubular drug vinblastine sulfate on the ultrastructure of mouse hepatocytes was studied by thin sectioning and freeze-fracturing after intravenous injection of the drug. The following cytoplasmic modifications occurred in the hepatocytes: storage of lipid droplets, heavy accumulation of autophagosomes and vacuoles with very low density lipoprotein (VLDL)-like vesicles, pathological changes in the mitochondria, and dilatation of the Golgi complexes. From 30 minutes onwards the bile canaliculi appeared altered. The tight junctions surrounding the bile canaliculi became permeable to lanthanum. This increased permeability was correlated with a disorganized arrangement of tight junctional strands and localized interruptions within the zonulae occludentes. In contrast to controls the gap junctions appeared more numerous and larger in size, exhibiting a high degree of pleomorphism. In the cytoplasm gap junctional vesicles could be observed indicating the removal of gap junctions from the surface by a process of internalization. We cannot establish whether the described changes are a direct or indirect effect of vinblastine sulfate treatment. In view of the antimicrotubular effect of vinblastine sulfate we hypothesize that normal formation of gap- and tight junctions is dependent directly or indirectly on intact microtubules.