Studies on vinblastine-induced autophagocytosis in the mouse liver.I. The relation of lysosomal changes to general injurious effects.

Abstract

Intraperitoneal injection of two doses of vinblastine (10 mg/kg and 50 mg/kg) induced a prominent formation of autophagic vacuoles in mouse liver parenchymal cells in 4 h. Clearly recognizable organelles were seen inside these vacuoles. The amount of autophagy was dependent on doses in that autophagosomes almost disappeared within 12 h with the low dose, whereas with the high dose the -ells were filled with residual bodies. Defecation of lysosomal material was ovserved into the sinusoidal lumen 12 h after injection with high dose. The total activities of lysosomal enzymes acid phosphatase, beta-galactosidase, and beta-acetylglucosaminidase did not change in the liver after vinblastine administration. The soluble activities of beta-galactosidase and beta-glucosaminidase were elevated with the high dose 12 h after injection, indicating labilization of the lysosomal membranes. Simultaneously the activities of the three lysosomal enzymes were elevated in the serum. The injurious effect of VBL appeared in light-and electron microscopic levels indicating diffuse necrosis of the liver lobules with the high gose within 12 h, fat accumulation in the cells, accumulation of secretory vesicles containing very low density lipoprotein particles, partial dilatation, vesiculation of endoplasmic reticulum and dilatation of Golgi cisternae. The serum GOT and CPK levels were also elevated