Acta Neuropathologica

, Volume 39, Issue 2, pp 147–155 | Cite as

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

  • Noritsugu Mukai
  • Takashi Nakajima
  • Thomas Freddo
  • Margaretha Jacobson
  • Mary Dunn
Original Investigations


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.

Key words

C3H/BifB/Ki strain mice Human adenovirus 12 Retinoblastoma-like neoplasm Immunofluorescein T-antigens Intracytoplasmic cilia C particle-like virions 


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  1. Bernhard, W.: Oncorna viruses. 2. Type A and C virus particles in murine and other mammalian leukemias and sarcomas. In: Ultrastructure of animal viruses and bacteriophages: An atlas. (eds. A. J. Dalton and F. Haguenau), pp. 283–304. New York: Academic Press 1973Google Scholar
  2. Bishop, J. O., Madson, E. C.: Retinoblastoma. Review of the current status. Survey Ophthalmol.19, 342–366 (1975)Google Scholar
  3. Chino, F., Tsuruhara, T., Egashira, Y.: Pathological studies on the oncogenesis of adenovirus type 12 in hamsters. Jpn. J. Med. Sci. Biol.20, 483–500 (1967)Google Scholar
  4. Espiritu, R., Tan, J.: Retinoblastoma in the Philippines. Meeting of Philippine Ophthal. Otolaryngol. Soc., Manila, Feb. 1967Google Scholar
  5. Huebner, R. J., Rowe, W. P., Lane, W. T.: Oncogenic effects in hamsters of human adenovirus type 12 and 18. Proc. Natl. Acad. Sci. (U.S.A.)48, 2051–2058 (1962)Google Scholar
  6. Jensen, R. D., Miller, R. W.: Retinoblastoma: Epidemiologic characteristics. New Eng. J. Med.285, 307–311 (1971)Google Scholar
  7. Kawamura, A., Jr.: Fluorescent antibody technique and their applications. Tokyo: Univ. Tokyo Press 1969Google Scholar
  8. Knudson, A. G., Jr.: Mutation and cancer: Statistical study of retinoblastoma. Proc. Natl. Acad. Sci. (U.S.A.)68, 820–823 (1971)Google Scholar
  9. Knudson, A. G., Jr., Hethcote, H. W., Brown, B. W.: Mutation and childhood cancer: A probabilistic model for the incidence of retinoblastoma. Proc. Natl. Acad. Sci. (U.S.A.)72, 5116–5120 (1975)Google Scholar
  10. Kobayashi, S., Mukai, N.: Retinoblastoma-like tumors induced in rats by human adenovirus. Invest. Ophthalmol.12, 853–856 (1973)Google Scholar
  11. Kobayashi, S., Mukai, N.: Retinoblastoma-like tumors induced by human adenovirus type 12 in rats. Cancer Res.34, 1646–1651 (1974)Google Scholar
  12. Liebelt, A. G., Kling, M., Liebelt, R. A.: Information on mouse colony of Kirschbaum Memorial Laboratory, Medical College of Georgia, Augusta. Modified from: Inbred strains of mice No. 7. Companion to Mouse Newsletter No. 45, July 1971. The Jackson Laboratory, Bar Harbor, MaineGoogle Scholar
  13. Mukai, N.: Retinoblastoma: Virus-induced retinal tumors. Jpn. J. Ophthalmol.19, 94–101 (1975)Google Scholar
  14. Mukai, N.: Human adenovirus-induced embryonic neuronal phenotype in rodents. In: Progress in neuropathology, vol. 3 (ed. H. M. Zimmerman), pp. 89–128. New York: Grune & Stratton 1976Google Scholar
  15. Mukai, N., Kobayashi, S.: Primary brain and spinal cord tumors induced by human adenovirus type 12 in hamsters. J. Neuropathol. Exp. Neurol.32, 523–542 (1973a)Google Scholar
  16. Mukai, N., Kobayashi, S.: Human adenovirus-induced medullo-epitheliomatous neoplasms in Sprague-Dawley rats. Am. J. Pathol.73, 671–690 (1973b)Google Scholar
  17. Mukai, N., Kobayashi, S., Murao, T.: Human adenovirus-produced neuronal tumor phenotype in the central nervous system of C3H/He and C3H/BifB/Ki mice. Unpublished observationsGoogle Scholar
  18. Mukai, N., Kobayashi, S., Oguri, M.: Ultrastructural studies of human adenovirus-produced retinoblastoma-like neoplasms in Sprague-Dawley rats. Invest. Ophthalmol.13, 593–601 (1974a)Google Scholar
  19. Mukai, N., Kobayashi, S., Oguri, M.: Ultrastructural findings in medullo epitheliomatous neoplasms induced by human adenovirus 12 in rodents. Acta neuropathol. (Berl.)28, 293–304 (1974b)Google Scholar
  20. Mukai, N., Kobayashi, S., Murao, T.: Cellular monstrosity in embryonic neuronal neoplasm produced by human adenovirus in rats. Acta neuropathol. (Berl.)30, 315–328 (1974)Google Scholar
  21. Mukai, N., Murao, T.: Retinal tumor induction by ocular inoculation of human adenovirus in 3-day-old rats. J. Neuropathol. Exp. Neurol.34, 28–35 (1975)Google Scholar
  22. Murao, T.: Induction of intracranial tumors in mice by human adenovirus type 12. I. Immunofluorescent studies on T-antigen and the predilection sites for tumor development in the brain. Acta Path. Jpn22, 41–51 (1972)Google Scholar
  23. Murao, T., Ohmori, H., Sonobe, H., Matsuo, K., Tsutsumi, A., Ogawa, K.: Brain tumors induced in rats by human adenovirus type 12. Acta Med. Okayama28, 47–58 (1974)Google Scholar
  24. Ogawa, K., Hamaya, K., Fujii, Y., Matsuura, K., Endo, T.: Tumor induction by adenovirus type 12 and its target cells in the central nervous system. Gann60, 383–392 (1969)Google Scholar
  25. Ogawa, H.: Pathological investigations on adenovirus type 12-induced hamster brain tumors — Localization of tumor cells at the initial stages. (in Japanese) Niigata Univ. Med. J.87, 297–310 (1973)Google Scholar
  26. Rabson, A. S., Kirschstein, R. L., Paul, F. J.: Tumors produced by adenovirus 12 in mastomys and mice. J. Natl. Cancer Inst.32, 77–87 (1964)Google Scholar
  27. Reid, T. W., Albert, D. M., Rabson, A. S., Russell, P., Craft, J., Chu, E. W., Tralka, T. S., Wilcox, J. L.: Characteristics of an established cell line of retinoblastoma. J. Natl. Cancer Inst.53, 347–360 (1974)Google Scholar
  28. Verhoeff, F. H., Jackson, E.: Cited in: Minutes of the proceedings. Sixty-second Annual Meeting, Trans. Am. Ophthalmol. Soc.24, 33–54 (1926)Google Scholar
  29. Zimmerman, L. E.: Retinoblastoma. In: Ophthalmic pathology. An atlas and textbook (eds M. J. Hogan and L. E. Zimmerman), pp. 516–525. Philadelphia: W. B. Saunders 1962Google Scholar

Copyright information

© Springer-Verlag 1977

Authors and Affiliations

  • Noritsugu Mukai
    • 1
  • Takashi Nakajima
    • 1
  • Thomas Freddo
    • 1
  • Margaretha Jacobson
    • 1
  • Mary Dunn
    • 1
  1. 1.Wesley C. Bowers Laboratory of Pharmacology and Experimental PathologyEye Research Institute of Retina FoundationBostonUSA

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