Ultrastructural changes of the vascular endothelium after intra-arterial administration of tumor necrosis factor-alpha (TNF alpha) in rat gliomas

The ensuing ultrastructural changes in tumor Vascular endothelial cells fol lowing intra-arterial administration of tumor necrosis factor-alpha (TNF al pha) were studied in an experimental rat glioma model. C6 glioma cells were implanted in Wistar rats and then after 14 days, 5 x 10(3) U of human natu ral-type TNF alpha (1.7 x 10(5) U/m(2)) was administered through the caroti d artery. The animals were sacrificed at 3 or 24 h after TNF alpha treatmen t. A detailed examination with transmission electron microscope revealed sw elling of the tumor vascular endothelial cell nuclei and mitochondria with matrix densities at 3 h. At 24 h, these cells demonstrated the presence of high amplitude mitochondrial swelling or the violent blebbing characteristi c of damaged mitochondria; the cytoplasm was swollen enormously and there w ere dissolution of cytoplasmic organelles and rupture of the plasma membran e. The observed findings were typical of cell necrosis and confirms yet ano ther mechanism by which TNF alpha exerts its anti-tumor effects, that is, n ecrotizing effects on tumor vascular endothelium. The information appears t o be important in the context of clinical application of intra-arterial TNF alpha in the treatment of malignant gliomas.