Early stage of human adenovirus type 12-inoculated retinal tissue of F344 newborn rat.

Abstract

To elucidate the pathogenesis of adenovirus type 12 (Ad12)-induced rat retinal tumor, an experimental animal model of human retinoblastoma (RB), DNA analysis, in situ hybridization and immunohistochemistry were performed. The adenovirus oncogene E1A was detected in the host genome by Southern blot hybridization. Examined retinal tissues did not show any histological changes, but the number of retinal cells immunoreactive with an antibody to proliferating cell nuclear antigen (PCNA) increased with the course of study. In in situ hybridization, E1A gene expression was recognized at the inner granular layer of the retina at an early stage after virus inoculation, and subsequently, N-myc gene expression was recognized at the same region. No alteration was found in the retinoblastoma susceptibility gene (Rb gene) expression. The product of the virus oncogene integrated into the host genome could induce an increase in N-myc expression, without any abnormality of the Rb gene itself. Results from the present study could be useful in clarifying the tumorigenesis of this experimental model.