Retinoblastoma-like tumors induced by human adenovirus type 12 in rats.
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Biomedical subjects
Publications and source records attributed to N Mukai.
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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.
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A single intraperitoneal inoculation of 0.01 ml of virus fluid, 10(3.5) to 10(4.5) TCID(50) HeLa cells/0.1 ml, was made in 12 newborn hamsters. From 28 to 96 days after the virus inoculation, all 12 hamsters developed multiple, multicentric tumors in the peritoneal cavity. Histopathologic observations on these abdominal tumors strongly suggest that the so-called adenovirus-typical undifferentiated neoplasm produced by intraperitoneal inoculation may originate in part from a neuronal precursor cell group destined for the myenteric plexus. A histochemical study has indicated no direct evidence that the intracytoplasmic basophilic corpuscle is comparable to that of the enterochromaffin pigment. A cytologic perusal under electron microscopy has merely suggested that the poorly differentiated tumor cells closely resemble those described in undifferentiated neurogenic tumors. The mechanism of selective susceptibility of certain neuronal precursor cells to adenovirus remains unanswered.
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