Radiosensitivity and Biological Properties of Two Tumour-types Indigenous to the Same Host

Summary

Studies have been carried out on effects of x-radiation on intracellular fine structures and on ATPase activity of cell nuclei and of mitochondria. Two types of mouse mammary tumours—epithelial, designated H, and spindle-cell, designated G, both indigenous to the inbred DBA/212 strain of mice—served as the basic test material. Mouse lymph-nodes were used for control tissue.

The tissues were irradiated in situ with various doses of 200 kv, filtered x-rays and excised at various time-intervals after irradiation for analytical and cytological studies. Ultra-centrifugation procedures were used for isolation of sub-cellular units, and electron microscopy for identification of cellular ultra-structures.

A significant, quantitative difference in the inherent mitochondrial and nuclear ATPase activities of these two types of tumour was noted. The inherent mitochondrial ATPase of the epithelial tumour was 62 per cent higher than that of the spindle-cell tumour. This difference is explained by the greater number and better quality of the mitochondria of the epithelial tumour, compared with those of the spindle-cell tumour, as revealed electron-microscopically. Conversely, the non-irradiated nuclear ATPase activity of the spindle-cell tumour was 20 per cent greater than that of the epithelial tumour. This difference was explained by the larger size of the spindle-cell tumour-nuclei. The effects of x-irradiation on nuclear and mitochondrial ATPase activity of both types of tumour are shown.

Electron-microscopic studies revealed profound changes in the sub-cellular units of the irradiated tumour cells, such as swelling of mitochondria, ruptures of their limiting and internal membranes (cristae), dilatation of the vesicles of the endoplasmic reticulum, ruptures of the plasma membranes and aggregation of the ribonucleoprotein (RNP) particles. These phenomena were more prevalent in the spindle-cell tumour after irradiation with 3000 than in the epithelial after 5000 rads.

Similar manifestations, but more dramatic and to a greater extent, were produced in the cells of the lymph-nodes after irradiation with relatively small doses (400 rads). Whereas the earliest profound changes induced by x-irradiation were noted in the sub-cellular units of the cytoplasm, no apparent changes were noted in the interphase nuclei. The plasma cells which are characterized as rich in vesicles of the endoplasmic reticulum and poor in mitochondria proved to be the most radiosensitive.