Retinoblastoma-like neoplasm induced in C3H/BifB/Ki strain mice by human adenovirus serotype 12

Abstract

Eighty newborn C3H/BifB/Ki strain mice received a single intraocular inoculation of 0.002--0.003 ml of 10(8.0) TCID 50/0.1 ml human adenovirus 12 (AD 12), within 24 h after birth. Forty mice survived and in seven of these (17.5%) a solid retinoblastomalike neoplasm developed between 64 and 236 days. The tumors have been successfully cultured and also transplanted subcutaneously into syngeneic hosts. Morphologically, all tumors revealed characteristic features of retinoblastoma associated with the Homer Wright type of rosettes. Bizarre giant cells were commonly detectable. Ad 12-specific T-antigens were demonstrated in both the primary and cultured tumor cells using immunofluorescent techniques. Some giant cells also showed numerous T-positive filaments. Electron microscopy disclosed poorly differentiated unipolar cells possessing a large ovoid nucleus. Many tumor cells appeared to contain a well organized solitary cilium consisting of a typical ring of nine doublets with no axial (9 + 0) in close association with a pair of centrioles. Some multinucleated giant tumor cells also contained multiple cilia-centriole complexes within their broad syncytial cytoplasm. Occasional endogenous C particle-like virions unique to murine neuroblastomas were observed for the first time in virus-induced retinal tumors. This unprecedented tumor model in a pure strain mouse adds to the range of known animals sensitive to Ad 12 oncogenesis.