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Retinoblastoma-like neoplasm induced in C3H/BifB/Ki strain mice by human adenovirus serotype 12
Authors:Noritsugu Mukai  Takashi Nakajima  Thomas Freddo  Margaretha Jacobson  Mary Dunn
Institution:(1) Wesley C. Bowers Laboratory of Pharmacology and Experimental Pathology, Eye Research Institute of Retina Foundation, 02114 Boston, Massachusetts, USA;(2) Present address: Harvard Medical School (Neuropathology and Neuro-Ophthalmology), Boston, USA;(3) Editorial Services Unit, Eye Research Institute of Retina Foundation, 02114 Boston, Massachusetts, USA
Abstract:Summary Eighty newborn C3H/BifB/Ki strain mice received a single intraocular inoculation of 0.002–0.003 ml of 108.0 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 retinoblastoma-like 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 pair (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.This work was supported in part by PHS research grant EY-01667 from the U.S. National Eye Institute (Dr. Mukai), grants from the Retina Research Foundation, Houston, Texas, U.S.A. (Dr. Mukai), the Massachusetts Lions Eye Research Inc., Research to Prevent Blindness, Inc., New York, and Fight for Sight, Inc., New York (Dr Nakajima)
Keywords:C3H/BifB/Ki strain mice  Human adenovirus 12  Retinoblastoma-like neoplasm  Immunofluorescein T-antigens  Intracytoplasmic cilia  C particle-like virions
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