Ultrastructural alterations in the mouse liver following vincristine administration.

The damage pattern in mouse liver was investigated following a single administration of 0.15 mg vincristine sulfate using the conventional thin-section technique and freeze-fracture. Numerous cytoplasmic changes were observed. Foremost of these was the increase in autophagosomes and vacuoles with very-low-density-lipoprotein (VLDL)-like vesicles. The rough endoplasmic reticulum exhibited a vesicular structure. The mitochondria also exhibited alterations such as enlargement and polymorphism. Both the interstitium and bile canaliculi were dilated. Lanthanum penetrated into the lumen of the canaliculi, i.e. the sinusoid/canaliculus compartmentalization did not remain intact, thus permitting bile to pass into the blood. Of particular significance are the alterations in the intercellular junctions. In contrast to the controls, the tight junctions were reduced and irregularly arranged. The gap junctions exhibited hypertrophy as well as a very irregular contour. The alterations may either be attributed to non-specific toxic effects of vincristine and/or the destructive properties of the agent on microtubules.