Primary Brain and Spinal Cord Tumors Induced by Human Adenovirus Type 12 in Hamsters

Abstract

Twenty-nine (37%) of 78 newborn hamsters developed an autochthonous malignant tumor of the central nervous system within 31 to 204 days after a single intracerebral inoculation of 0.01 ml of virus fluid, containing 10^3.5–10^4.5 TCID50 HeLa cells/0.1 ml. Eight solid tumors protruding into the ventricular system developed in the left cervical hemisphere where the virus was inoculated. In one case, entirely separate tumors were found in both hemispheres. Four were small incipient neoplasms located immediately adjacent to the ventricular system. Two appeared to block entirely the IVth ventricle. Three were situated in the medulla oblongata. Sixteen spinal cord tumors were found, mainly in the dorsal half of the column, without extension to the leptomeninges. Histopathological studies of all of these tumors showed a remarkable uniformity. The tumors were designated as the counterpart of human embryonic gliomas derived from the ependymal analge. Electron microscopy clearly revealed a single cilium with a typical concentric pattern of nine pairs of peripheral doublets with no central pair (9 + 0) in the apical processes of many tumor cells. The presence of cilia of neuronal origin suggests that these tumor cells mimic certain developing neurons (chiefly sensory). The presence of numerous intracytoplasmic filaments and microtubules in dysplastic neuronic cells also suggested a neuronal origin. Detection of immunofluorescent T-antigen in frozen sections confirmed the viral origin of the tumor. Subcutaneous transplantation of the tumor gave rise to rapid neoplastic growth in recently weaned hamsters. Control animals inoculated with the culture media developed no tumors.