Effects of Hyperthermia on the Ultrastructure of Spontaneous Mouse Mammary Tumors with Reference to Viral Dysmorphogenesis

Abstract

The mechanisms of cell death by hyperthermia were investigated in the spontaneous mammary tumors of the Strong A strain of mice. Circulating hot-water in a latex bag was used to apply a local heat dose of 46uC for 1 hour to the tumors in anaesthetized mice. The tumors were surgically removed from the mice under anesthesia at various times after heat treatment and studied by electron microscopy. Cytoplasmic swelling and condensation of nuclear chromatin occurred 5 minutes after heat treatment. Degenerative changes then became progressively more pronounced at 24, 48, and 72 hours after heat treatment. This included disorganization of the cytoplasm and loss of organelles, a marked increase in the number and size of lysosomes, the disruption of plasma membranes, the loss of nuclear membranes, nucleoli, and the fragmentation of condensed chromatin. There was also infiltration by granulocytes, and bundles of collagen fibrils into the tumor tissue. The mouse mammary tumor virus particles in the heated tumor cells were deformed and turned into amorphous masses. Our findings suggest that heat induced degenerative changes in the spontaneous mouse mammary tumors occurs through a combination of mechanisms including mitochondrial damage, rupture of cell membranes, damage to nuclei, and a marked increase in lysosomal activity, the latter playing the primary role in the hyperthermic killing of malignant cells.