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

Mohinder S. Jarial, Duncan T. Kennedy, John H. Wilkins

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.

Keywords


Hyperthermia, plasma membranes, lysosomes, mitochondria and chromatin

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