Retinal tumor induction by ocular inoculation of human adneovirus in 3-day-old rats

Abstract

A direct causal relationship between a human DNA virus, adeno serotype 12, and malignant transformation in target cells (sensory retinal neuronal precursors) was suggested by the development of a remarkably uniform retinoblastoma-like neoplasm in rats. In order to focus upon incipient photoreceptor differentiation, 27 3-day-old CD rats were selected for intraocular virus inoculation. A single injection of 0.03 ml of the virus fluid, 104.5 TCID50 HeLa cells/0.1 ml was given in the left eye. Within 73 to 167 days after the virus inoculation, 12 rats (44.4%) developed retinal tumors in the left eye. Although retinal tumors mimicking human retinoblastoma with true rosettes were anticipated, the highly uniform histopathologic appearance of all 12 eyes was virtually indistinguishable from that of 0-day-old rats. However, multiple foci of malignant cells fusing with the inner segment of relatively well-differentiated retinal layers were found haphazardly throughout the cases; such retinal remnants were not detectable in tumors of 0-day-old rats. Electron microscopy revealed poorly differentiated tumor cells that possessed a single cilium consisting of a typical ring of nine doublets with no axial pair (a 9 plus 0 pattern). Advenovirus-specific T-antigens detected in vivo by the immunofluorescein microscopic procedure in abortively infected or transformed cells clearly indicated that some neuronal precursors destined for part of the ganglioneuronic layer are selectively susceptible to viral oncogenesis. No preferential involvement of the photoreceptor cells was observed. No control animals developed retinal neoplasms.