Ultrastructure of a murine mammary carcinoma exposed to hyperthermia in vivo.

The ultrastructural changes following local hyperthermic therapy was studied in a solid murine mammary carcinoma. A few hr after treatment, a pronounced lysosomal activity was observed in the cytoplasm of the tumor cells, together with mitochondrial destruction and disaggregation of the polyribosomes. Later, more destructive changes with intense cell shrinkage and cytoplasmic lysis occurred, and within 24 hr the entire cytoplasm of all the tumor cells was completely destroyed. In the nuclei shrinkage and condensation of heterochromatin were early features. The nucleoli were gradually degranulated, but with preservation of the fibrillary component. However, here, too, complete destruction occurred within the first few days after treatment. Cells in mitosis were also arrested and destroyed in the same way. The nonmalignant cells of the tumor tissue presented only minor reversible morphological changes, and within a few days the tumor area was replaced by ingrowth of fibroblasts and macrophages. The morphological changes are discussed in the light of our present knowledge of the hyperthermic effect on tumor cells. As regards the mechanism of hyperthermic destruction of solid tumors in vivo, the hypothesis is advanced that a primary, lysosomally conditioned, selective destruction of the malignant cells occurs and that this reaction is intensified by a high acidity in the tumor milieu.