Light and electron microscope study of osmotically induced tumor necrosis

Necrosis of 1.5-cm Walker 256 tumors was produced by injecting a strongly hypertonic solution of glucose in and around the growths and by delaying resorption of the solution with serotonin, given s.c. at a distance. The morphological changes occurring in 13 tumors were followed by light and electron microscopic analysis of samples taken 0.25, 0.5, 1, 1.5, 3, and 5 hr after treatment. The 0.25-hr samples showed mitochondrial swelling, loss of cristae, and flocculent material within the inner compartment. Swelling of the mitochondria persisted in the 0.5-hr specimens (as it did in all subsequent samples), and it was accompanied by clumping and margination of chromatin. These changes were more pronounced at 1 hr, at which time the nuclear and plasma membranes were frequently ruptured. The endoplasmic reticulum and Golgi complex could no longer be recognized. The 3-hr material revealed ruptures of the outer mitochondrial membrane with myelin figures and discontinuous cell membranes. In the 5-hr samples, the nuclei exhibited a dark nucleoplasm and large clumps of chromatin. The perinuclear membrane was not always recognizable.