Combined effects of vinblastine and vincristine on mouse hepatocytes with respect to ultrastructural elements

The results of a single dose of the microtubule-destroying agents vinblastine/vincristine (0.5 mg/0.05 mg) on the ultrastructural elements of mouse hepatocytes was studied using the techniques of thin-sectioning and freeze-fracture following intravenous injection of the drugs. Several cytoplasmic modifications were observed in the hepatocytes. These included the storage of lipid droplets, a heavy accumulation of autophagosomes and vacuoles with very low density lipoprotein (VLDL)-like vesicles, large glycogen fields and dilated intercellular spaces with intrahepatocytic vacuoles. The rough endoplasmic reticulum exhibited pathological changes with loss of ribosomes and the bile canaliculi exhibited in some cases the loss of microvilli as well as dilatation of the lumen. The tight junctions surrounding the bile canaliculi exhibited alterations as well. The strands were reduced in number and showed a less organized arrangement. The gap junction showed an increase in size as well as an irregular outline in contrast to controls. These findings are interpreted as non-specific toxic phenomena. However, the possibility cannot be precluded that certain phenomena, such as alterations in the cell junctions, may be attributable to specific microtubule-destroying properties of the drugs.