Genomic DNA analysis of rat retinal tumor induced by adenovirus type 12.

To elucidate the pathogenesis of human retinoblastoma, we investigated the genomic expression in retinal tumors induced by human adenovirus type 12 in rats, using various DNA probes. Seven rats received a single intraocular inoculation of concentrated virus fluid within 24 hours after birth. Intravitreous tumors were induced in two out of seven animals (28.5%) within 30 to 64 days after the inoculation. A remarkably uniform histologic feature, i.e., neuroblastic cells in association with Homer-Wright pseudorosettes, was present in all cases. The adenovirus-related oncoprotein gene E1A and human retinoblastoma susceptibility gene were detected in the tumors by Southern blot hybridization. In situ hybridization analysis demonstrated expression of adenovirus type 12 E1A gene in the inner granular layer of the retina. It was suggested that integration of adenovirus type 12 E1A fragment with the host genome and expression of the gene were required for induction of this tumor.