Summary
Solid medullary brain and spinal cord neoplasms developed in all 10 offspring of an outbred Sprague-Dawley rat, between 37 and 99 days after a single postnatal (within 24 hrs) inoculation of 0.05 ml of human adenovirus type 12, 103.5–104.5 TCID50 HeLa cells/0.1 ml in the left frontal lobe. Seven rats developed multicentric neoplasms in both hemispheres and in peri-aqueductal areas of the brain stem, one of which was associated with an incipient spinal cord tumor in the sacral segment. One rat developed a solid tumor involving the right parieto-occipital region. The remaining two cases were solid spinal cord tumors arising from the dorsal half of the thoracolumbar segments. The remarkably uniform microscopic appearance was designated as a counterpart of human embryonic neuronal neoplasms. Characteristic neuronal and multinucleated giant cells emerged throughout the tumor tissue with argentaffine, neurofibril-like cytoplasmic expansions and a unique cilium (a 9+0 pattern of tubules) associated with a pair of centrioles. This cilium morphology was also a hallmark of the majority of tumor cells that formed characteristic pseudorosettes. The occasional emergence of two sets of cilia and centrioles in monstrous cells suggested probable modes of cytogenesis in relation to cessation of abnormal cell division.
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References
Allen, R. A.: Isolated cilia in inner retinal neurons and in retinal pigment epithelium. J. Ultrastruct. Res.12, 730–747 (1965)
Balazs, R.: Hormones and brain development. New Scientist58, 96–98 (1973)
Barnes, B. G.: Ciliated secretory cells in the pars distalis of the mouse hypophysis. J. Ultrastruct. Res.5, 453–467 (1961)
Dahl, H. A.: Fine structure of cilia in rat cerebral cortex. Z. Zellforsch.60, 369–386 (1963)
Deck, J. H.: Cerebral medulloepithelioma with maturation into ependymal cells and ganglion cells. J. Neuropath. exp. Neurol.28, 442–454 (1969)
Duncan, D., William, V., Morales, R.: Centrioles and cilia-like structures in spinal gray matter. Tex. Rep. Biol. Med.21, 185–187 (1963)
Dyke, P. C., Mulkey, D. A.: Maturation of ganglioneuroblastoma to ganglioneuroma. Cancer20, 1343–1349 (1967)
Fawcett, D. W.: Cilia and flagella. In: The Cell, Vol. 2, pp. 217–297. J. Brachet and A. E. Mirsky, eds. New York-London: Academic Press 1961
Green, M., Fujinaga, K., Pina, M., Thomas, D. C.: Molecular basis of viral oncogenesis. In: Exploitable molecular mechanisms and neoplasia, pp. 479–506. Baltimore: Williams and Wilkins Co. 1969
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)
Hart, M. N., Earle, K. M.: Primitive neuroectodermal tumors of the brain in children. Cancer32, 890–897 (1973)
Hogan, M. J., Alvarado, J. A., Weddel, J. E.: Histology of the Human Eye; An Atlas and Textbook, pp. 424–444. Philadelphia: W. B. Saunders Co. 1971
Jellinger, K.: Cerebral medulloepithelioma. Acta neuropath. (Berl.)22, 95–101 (1972)
Karch, S. A., Urich, H.: Medulloepithelioma: Definition of an entity. J. Neuropath. exp. Neurol.31, 27–53 (1972)
Karnovsky, M. J.: A formaldehyde-glutaraldehyde fixative of high osmolarity for use in electron microscopy. J. Cell Biol.27, 137 A (abstract) (1965)
Kirschstein, R. L., Rabson, A. S., Paul, F. J., Peters, E. A.: Double infection of newborn Syrian hamsters with simian virus 40 and human adenovirus 12. Cancer Res.26, 1361 to 1364 (1966)
Kobayashi, S., Mukai, N.: A sequential study of tumor specific T-antigens in newborn rats following single intracerebral inoculation of human adenovirus 12. Unpublished data (1972)
Kobayashi, S., Mukai, N.: Retinoblastoma-like tumors induced in rats by human adenovirus. Invest. Ophthal.12, 853–856 (1973)
Kobayashi, S., Mukai, N.: Retinoblastoma-like tumors induced by human adenovirus type 12 in rats. Cancer Res.34, 1646–1651 (1974)
Mukai, N., Kobayashi, S.: Undifferentiated intraperitoneal tumors induced by human adenovirus type 12 in hamsters. Amer. J. Path.69, 331–348 (1972)
Mukai, N., Kobayashi, S.: Extraocular orbital tumors induced by human adenovirus type 12 in hamsters. Invest. Ophthal.12, 185–192 (1973a)
Mukai, N., Kobayashi, S.: Primary brain and spinal cord tumors induced by human adenovirus type 12 in hamsters. J. Neuropath. exp. Neurol.32, 523–541 (1973b)
Mukai, N., Kobayashi, S.: Human adenovirus-induced medulloepitheliomatous neoplasms in Sprague Dawley rats. Amer. J. Path.73, 671–690 (1973c)
Mukai, N., Kobayashi, S.: Ultrastructural studies of human adenovirus-produced retinoblastoma-like neoplasms in Sprague Dawley rats. Invest. Ophthal.13, 593–601 (1974b)
Mukai, N., Kobayashi, S., Oguri, M.: Ultrastructural findings in medulloepitheliomatous neoplasm induced by human adenovirus 12 in rodents. Acta neuropath. (Berl.)28, 293–304 (1974)
Mukai, N., Murao, T.: Retinal tumor induction by ocular inoculation of human adenovirus in 3-day-old rats. J. Neuropath. exp. Neurol., (in press) (1974)
Murao, T.: Induction of intracranial tumors in mice by human adenovirus type 12. II. Enhancement by N,N′-Dimethylnitrosourea. Acta Med. Okayama25, 261–268 (1971)
Ogawa, K., Tsutsumi, A., Iwata, K., Fujii, Y., Ohmori, M., Taguchi, K., Yabe, Y.: Histogenesis of malignant neoplasm induced by adenovirus type 12. Gann57, 43–52 (1966)
Ogawa, K., Fujita, H., Motoi, M., Akagi, T., Yabe, Y.: Incubation period for tumor induction by adenovirus type 12. Gann58, 247–251 (1967)
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)
Pereira, M. S., MacCallum, F. O.: Infection with adenovirus type 12. Lancet1964I, 198–199
Pope, J. H., Rowe, W. P.: Immunofluorescent studies of adenovirus 12 tumors and of cell transformed or infected by adenoviruses. J. exp. Med.120, 577–588 (1964)
Rapp, F., Pauluzzi, S., Waltz, T. A., et al.: Induction of brain tumors in newborn hamsters by simian adenovirus SA7. Cancer Res.29, 1173–1178 (1969)
Rubinstein, L. J.: Cytogenesis and differentiation of primitive central neuroepithelial tumors. J. Neuropath. exp. Neurol.31, 7–26 (1972)
Russel, D. S., Rubinstein, L. J.: Pathology of tumors of the nervous system, pp. 156–172. Baltimore: Williams and Wilkins Co. 1963
Sotelo, J. R., Trujillo-Cenoz, O.: Electron microscopic study on the development of ciliary components of the neural epithelium of the chick embryo. Z. Zellforsch.49, 1–12 (1958)
Spjut, H. J., Van Hoosier, G. L., Trentin, J. J.: Neoplasms in hamsters induced by adenovirus type 12. Arch. Path.83, 199–203 (1967)
Stair, P.: Cilia. In: The living cell, pp. 53–61. San Francisco-London: W. H. Freeman Co. 1965
Trentin, J. J., Yabe, Y., Taylor, G.: The quest for human cancer viruses. Science137, 835–841 (1962)
Ts'o, M. O., Fine, B. S., Zimmerman, L. E.: The nature of retinoblastoma. II. Photoreceptor differentiation: An electron microscopic study. Amer. J. Ophthal.69, 350–359 (1970)
Treip, C. S.: A congenital medulloepithelioma of the midbrain. J. Path. Bact.74, 357–363 (1957)
Uga, S., Smelser, G. K.: Electron microscopic study of the development of retinal Müllerian cells. Invest. Ophthal.12, 295–307 (1973)
Yabe, Y.: Antibody to adenovirus type 12 among infants. Lancet1964I, 1447–1448
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Mukai, N., Kobayashi, S. & Murao, T. Cellular monstrosity in embryonic neuronal neoplasm produced by human adenovirus in rats. Acta Neuropathol 30, 315–328 (1974). https://doi.org/10.1007/BF00697014
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DOI: https://doi.org/10.1007/BF00697014