Metastatic brain tumors induced by injected of syngeneic tumor cells into cerebral circulation in rats.

Abstract

Adult lewis rats were injected with tissue cultured cells of a transplantable Lewis rat malignant schwannoma (ENU-induced) into the right internal carotid artery, right vertebral artery, the left ventricle of the heart, or the right femoral vein. Groups of animals received injections of 0.5×105; 1.5×105; 5×105; 10×105, or 100×105 viable cells, using each of these routes. In many animals, the injection was followed by development of metastases. Cerebral metastases developed using all three arterial routes. Injections into the carotid or vertebral artery with 5×105–100×105 cells were effective. With each of these routes, leptomeningeal carcinomatosis and perivascular “encephalitic-like” tumor growth were most frequently observed. Focal cerebral microor macrotumors were less common. With intracarotid injection, metastases were located mostly in the cerebral hemispheres and in the cerebral leptomeninges, particularly on the side of injection. Injection into vertebral artery resulted in metastases located mostly in the cerebellum, brain stem, or cerebellar leptomenges. With intracardiac injection, only one rat in 50 developed a single focal brain metastasis, although all these animals developed metastases in other organs. With i.v. injection all rats developed pulmonary metastases, although the total pulmonary tumor burden was conspicuous only with high doses of injected tumor cells. In addition, some of these animals also developed metastases in other internal organs, but the brain was nerver involved. Comparison was made of tumor induction with injection of the same doses of tumor cells by the various routes used.