Sequential development of hematogenous cerebral metastatic tumors in rats.

To study the sequential growth patterns of hematogenous cerebral metastatic tumors, syngenetic RG2 glioma cells were injected into the right common carotid artery of 61 adult CDF rats. Electron microscopic study 1 hr and 24 hrs after injection revealed arrested tumor cells in the capillaries, some with faint glial filaments in their cytoplasm. Perivascular edema of the right hemisphere which developed following occlusion of the right common carotid artery during injection was noteworthy concerning the attachment of the tumor cells to the capillary walls and their penetration into the perivascular spaces. Luminescence microscopic observation with acridine orange 1 hr and 24 hrs after injection showed circulating or embolized tumor cells in the capillaries, and about 5 days after injection, the cells began to penetrate the perivascular space. For light microscopic examination, 51 rats were sacrificed from 1 hour to 20 days after injection. From 9 days after injection on, microtumors began to appear and metastatic tumors developed in 76% of the right hemispheres, and in 57% of the left hemispheres. Considering all sections of the 21 rat brains from 9 to 20 days, the difference of tumor frequency between the right (42%) and left (19%) hemispheres became even more significant. Morpho metrical evaluation using a planimeter showed the growth curve of the tumor area to have a low pitch from 12 to 18 days which became steeper from 18 to 20 days. Synthesizing the results sequentially, the following five stages could be defined: 1) a silent period; 2) a penetrating and mitotic period; 3) a microtumor period; 4) a multiple proliferating period; and 5) an expanding period.