Human adenovirus-induced medulloepitheliomatous neoplasms in Sprague-Dawley rats.

Abstract

A direct causal relationship between a human virus and malignant transformations in target cells (sensory neuronal precursors) was suggested by the development of a medulloepitheliomatous neoplasm in the central nervous system. Twenty-six newborn Sprague-Dawley rats were given a single intracerebral inoculation of 0.05 ml of adenovirus fluid, 10(3.5) to 10(4.5) TCID(50) HeLa cells/0.1 ml, in the left frontal lobe. Within 37 to 151 days after the virus inoculation, 23 (88.7%) rats autochthonously developed an adenovirus-typical neoplasm in the central nervous system. Nine animals developed a multicentric neoplasm closely related to the ventricular system. Nine others developed solid variously sized neoplasms along the ventricular lumen. Some neoplasms showed multiple foci connected with the stratum subependymale ventriculi olfactorii and the velum medullare of the fourth ventricle. Six spinal cord tumors, located chiefly in the dorsal sensory column, developed within 37 to 61 days after intracerebral inoculation. The remarkably uniform histopathologic appearance of all 23 cases was attributed to a medulloepitheliomatous neoplasm derived from the ependymal anlage. Electron microscopy clearly revealed a solitary cilium within the apical region of many tumor cells. It consisted of a typical ring of nine doublets with no axial pair (a 9+0 pattern), the typical structure of cilia of sensory neuronal origin. The appearance of exuberant neuron-like tumor cells with argyrophile cytoplasmic expansions, neurosyncytial mosaic alignment and myelin-like configurations also suggested a neuronal origin. A paucity of mesenchymal stroma in the neoplastic tissue was noted. No control animals developed tumors.