Summary
The histology, ultrastructure, and nuclear RNA polymerase activity are described in a murine primitive neuroectodermal tumor derived by serial transplantation from a tumor originally induced with methylcholanthrene and classified as an ependymoblastoma. The light microscope and ultrastructural studies show that this tumor does not contain the distinguishing morphological features of differentiated ependymal cells which are also commonly seen in human ependymomas. One outstanding feature is the size and number of the nucleoti. The mean number of nucleoli/nucleus is 4 which is two to four times that of the normal neuroglial cell. The nucleolar diameter is about twice that found in normal neuroglial cells. The nuclear RNA synthesizing activity is the highest of the chemically induced animal tumors we have studied. The alpha amanitin inhibition is the lowest seen in any of these tumors which suggests that the RNA polymerases inhibited by alpha amanitin contribute less to the total nuclear RNA synthesis. Adriamycin significantly inhibits the nuclear RNA polymerase activity of this tumor.
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Albright, L., Madigan, J. C., Gaston, M. R., Houchens, D. P.: Therapy in an intracerebral murine glioma model, using Bacillus Calmette-Guerin, neuraminidase-treated tumor cells, and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea. Cancer Res.35, 658–665 (1975)
Ames, R. P., Rubin, R. C.: Morphology of virus-like particles persisting in murine ependymoblastoma in vitro. Cancer Res.30, 1142–1148 (1970)
Augusti-Tocco, G., Sato, G.: Establishment of functional clonal lines of neurons from mouse neuroblastoma. Proc. Natl. Acad. Sci. U.S.A.64, 311–315 (1969)
Ausman, J. L., Shapiro, W. R., Rall, D. P.: Studies on the chemotherapy of experimental brain tumors: Development of an experimental model. Cancer Res.30, 2394–2400 (1970)
Bernhard, W., Granboulan, N.: Electron microscopy of the nucleolus in vertebrate cells. In: The nucleus (Dalton, A. J., Haguenau, F., eds.), pp. 81–137, New York: Academic Press 1968
Bolognari, A.: Su alcuni aspetti struttural: ed ultrastructural: delle cellule tumrali con particulare riferimento of carcinoma di Walker. Biol. Lat. (Milano)12, 1015–1040 (1959)
Brightman, M. W., Palay, S. L.: The fine structure of ependyma in the brain of the rat. J. Cell Biol.19, 415–440 (1963)
Busch, H., Smetana, K.: Nucleoli of tumor cells. In: The nucleus, p. 448. New York: Academic Press 1970
Crook, L. E., Rees, K. R., Cohen, A.: Effect of daunomycin on the HeLa cell nucleic acid synthesis. Biochem. Pharmacol.21, 281–286 (1972)
De Harven, E.: The centriole and the mitotic spindle. In: The nucleus. (Dalton, A. J., Haguenau, F., eds.), pp. 197–224, New York: Academic Press 1968
DiMarco, A., Silverstrini, R., DiMarco, S., Dasdia, T.: Inhibiting effect of the new cytotoxic antibiotic daunomycin of nucleic acids and mitotic activity of HeLa cells. J. Cell. Biol.27, 545–550 (1965)
Dorigotti, L.: Studio al microscopio elettricodelle modificazioni indotte dalla daunomicina sulle cellule HeLa. Tumori50, 117–123 (1964)
Dudeck, L. E., Gargus, J. L., Congleton, G. F., Geran, R. I., Abbott, B. J.: An experimental brain tumor model for screening potential carcinostatie drugs. Proc. Am. Ass. Cancer Res.14, 34 (1974)
Friede, R. L., Pollak, A.: The cytogenetic basis for classifying ependymomas. J. Neuropathol. Exp. Neurol.37, 103–118 (1978)
Fu, Y. S., Chen, A. T. L., Kay, S., Young, H. F.: Is subependymoma (subependymal glomerate astrocytoma) an astrocytoma or ependymoma. Caneer34, 1992–2008 (1974)
Geran, R., Congleton, G. F., Dudeck, L. E., Abbott, B. J., Gargus, J. L.: A mouse ependymoblastoma as an experimental model for screening potential antineoplastic drugs. Cancer Chemotherapy Repts.4, 53–87 (1974)
Goebel, H. H., Cravioto, H.: Ultrastructure of human and experimental ependymomas. J. Neuropathol. Exp. Neurol.31, 54–71 (1972)
Granboulan, N., Riviere, M. R., Bernard, W.: Présence de particles d'aspect viral dans un sarcome greffable de la souris provoqué par le methylcholanthrene. Bull. Cancer (Paris)7, 291–307 (1960)
Hari, M. N., Earle, K. M.: Primitive neuroectodermal tumors of the brain in children. Cancer32, 890–897 (1973)
Hurano, A., Ghatak, N. R., Wisoff, H. S., Zimmerman, H. M.: Comparative ultrastructural study of ependymoma and ependymal cyst. Am. J. Pathol.62, 11a (1971)
Ikuta, F., Zimmerman, H. M.: Virus particles induced with carcinogenic hydrocarbons. Proc. Virchow Med. Soc. N.Y. Suppl.26, 393–415 (1968)
Ikuta, F., Zimmerman, H. M.: The viral particles in the reactive cells of the brain induced by chemical carcinogens. Int. J. Neurol5, 10–28 (1965)
Ikuta, F., Zimmerman, H. M.: Intramuscular precancerous lesions from hydrocarbons. Arch. Pathol. Lab. Med.78, 377–389 (1964)
Jänisch, W., Schreiber, D.: Experimental tumors of the central nervous system. First English edition. (Bigner, D., Swenberg, J. A., eds.), Kalamazoo MI: Upjohn 1977
Karasaki, S.: Electron microscope examination of the sites of nuclear RNA synthesis during amphibian embryogenesis. J. Cell Biol.26, 937–958 (1965)
Kawai, S., Ishida, Y., Nagashima, I., Sato, K., Niibe, H.: Experimental studies on brain tumors. Acta Pathol. Jpn.14, 311–344 (1964)
Kroh, H., Majdecki, T., Renkawek, K.: Ultrastructure of experimental brain gliomas in mice. Z. Krebsforsch.86, 159–168 (1973)
Lambertenghi-Deliliers, G.: Ultrastructural alterations induced in hepatic cell nucleoli by adriamycin. In: International symposium on adriamycin. (Carter, S. K., DiMarco, A., Krakoff, I. H., Mathé, G., eds.), pp. 26–34. New York: Springer 1972
Laurent, G., Atassi, G., Hildebrand, J.: Potentiation of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea by amphotericin B in murine ependymoblastoma. Cancer Res.36, 4—69—4073 (1976)
Leplus, R., Debray, J., Pinet, J., Bernhard, W.: Lésions nucléaires décelées au microscope electronique dans les cellules de lymmes malins chez l'homme. Compte Rend.253, 2788–2790 (1961)
Lindell, T. J., Weinberg, F., Morris, P. W., Roeder, R. G., Rutter, W. J.: Specific inhibition of nuclear RNA polymerase II by amanitin. Science170, 447–449 (1970)
Luse, S. A.: Electron microscopic studies of brain tumors. Neurology10, 881–905 (1960)
Luse, S.: Ultrastructural characteristics of normal and neoplastic cells. Prog. Exp. Tumor Res.2, 1–35 (1961)
Menon, I. A.: Properties of RNA polymerase from a transplantable brain tumor. Brain Res.42, 529–533 (1972)
Miller, C. A., Thorack, R. M.: Secretory ependymoma of the filum terminale. Acta Neuropathol. (Berl.)15, 240–250 (1970)
Moore, D. H., Charney, J., Lasfarques, E. Y., Sarkar, N. H., Rubin, R. C., Ames, R. P.: Mammary tumor virus virions in a transplantable ependymoblastoma. Proc. Soc. Exp. Biol. Med.132, 125–127 (1969)
Parker, J. C., Mortara, R. H., McCloskey, J. J.: Biological behaviour of the primitive neuroectodermal tumors: significant supertentorial childhood gliomas. Surg. Neurol.4, 383–388 (1975)
Peers, J. H.: The response of the central nervous system to the application of carcinogenic hydrocarbons II methylcholanthrene. Am. J. Pathol.16, 799–816 (1940)
Penman, S., Vesco, C., Penman, M.: Locatization and kinetics of formation of nuclear heterodispersed RNA, cytoplasmic heterodispersed RNA, and polyribosome associated messenger RNA in HeLa cells. J. Mol. Biol.34, 49–69 (1968)
Popoff, N., Sutton, C. H., Zimmerman, H. M.: Virus-like particies in reactive cells associated with crystals of implanted carcinogen. Acta Neuropathol. (Berl.)10, 308–322 (1968)
Raimondi, J. A., Millan, S., Evans, P. J.: Human brain tumors: An electron microscope study. J. Neurosurg.19, 731–753 (1962)
Rawlinson, D. G., Herman, M. M., Rubinstein, L. J.: The fine structure of a myxopapillary ependymona of the filium terminale. Acta Neuropathol. (Berl.)25, 1–13 (1973)
Rubin, R. C., Ames, R. P.: Mammary tumor virus in experimental ependymoblastoma. Adv. Neurol.15, 335–349 (1976)
Rubin, R., Ames, R. P., Sutton, C. H., Zimmerman, H. M.: Virus-like particles in murine ependymoblastoma. J. Neuropathol. Exp. Neurol.28, 371–397 (1969)
Rubin, R., Sutton, C. H., Zimmerman, H. M.: Experimental ependymoblastoma. J. Neuropathol. Exp. Neurol.27, 421–438 (1968)
Rubinstein, L. J.: The definition of the ependymoblastoma. Arch. Pathol. Lab. Med.90, 35–45 (1970)
Rubinstein, L. J.: Cytogenesis and differentiation of primitive central neuroepithelial tumors. J. Neuropathol. Exp. Neurol.31, 7–26 (1972)
Rusconi, A., Calendi, E.: Action of daunomycin on nucleic acid metabolism. Biochim. Biophys. Acta119, 413–416 (1966)
Seligman, A. M., Shear, M. J., Alexander, L.: Studies in carcinogenesis. VIII. Experimental production of brain tumors in mice with methylcholanthrene. Am. J. Cancer.37, 364–399 (1939)
Shea, J. R., Leblond, C. P.: Number of nucleoli in various cell types of the mouse. J. Morphol.119, 425–434 (1966)
Shapiro, W. R., Ausman, J. L., Rall, D. P.: Studies on the chemotherapy of experimental brain tumors: evaluation of 1,3-Bis (2-chloroethyl)-1-nitrosourea, cyclophosphamide, mithramycin, and methotrexate. Cancer Res.30, 2401–2413 (1970)
Slagel, D. E., Akers, R. D.: Isolation, fractionation, and RNA polymerase activity in a sample enriched with oligodendroglial nuclei. Brain Res.44, 245–260 (1972)
Slagel, D. E., Norrell, H.: RNA polymerase activity in homotransplanted rat brain tumors initially induced by ethylnitrosourea. Acta Neuropathol (Berl)32, 1–7 (1975)
Studnička, F. K.: Umersuchungen über den Bau des Ependyms der nervösen Centralorgane. Anat. Hefte.15, 303–430 (1900)
Tani, E., Ametani, T.: Polygonal crystalline structures in human ependymoma cells. Acta Neuropathol. (Berl.)15, 359–362 (1970)
Tani, E., Higashi, N.: Intercellular junctions in human ependymomas. Acta Neuropathol. (Berl.)22, 295–304 (1972)
Tator, C. H., Day, A., Ng, R., Liberman, L.: Chemotherapy of an experimental glioma with nitrosoureas. Cancer Res.37, 476–481 (1977)
Tatsumi, K., Nakamura, T., Wakisaka, G.: Comparative effect of daunomycin and adriamycin on nucleic acid metabolism in leukemic cells in vitro. Gann65, 237–247 (1974)
Tennyson, V. M., Pappas, G. D.: An electron microscope study of ependymal cells of the fetal, early postnatal and adult rabbit. Zellforsch.56, 595–618 (1962)
Theologides, A., Yarbro, J. W., Kennedy, B. J.: Daunomycin inhibition of DNA and RNA synthesis. Cancer21, 16–21 (1968)
Torelli, U., Torelli, G., Mauri, C.: The macromolecular metabolism of ribosomal precursor RNA as a common target of different anti-tumor drugs. Eur. J. Cancer.8, 611–615 (1972)
Ushio, Y., Hayakawa, T., Mogami, H.: Uptake of tritiated methotrexate by mouse brain tumors after intravenous or intrathecal administration. J. Neurosurg.40, 706–716 (1974)
Wechsler, W.: Old and new concepts of oncogenesis in the nervous system of man and animals. In: Recent advances in brain tumor research. (Bingham, W. G., ed.). Prog. in Exp. Tumor Res.17, pp. 217–278, Basel: Karger 1972
Wechsler, W., Kleihues, P., Matsumoto, S., Zülch, K. J., Ivankovic, S., Preussman, R., Druckrey, H.: Pathology of experimental neurogenic chemically induced during prenatal and postnatal life. Ann. N.Y. Acad. Sci.159, 360–408 (1969)
Wessel, W.: Elektronenmikroskopische Beobachtungen von Zellveränderungen nach mehrtägiger Unterkühlung an Ascites-Tumorzellen sowie Vergleiche eines Ascitescarcinoms mit einem Ascitessarkom. Z. Krebsforsch.62, 675–693 (1959)
Wheatley, D. N.: Action of adriamycin on HeLa cells. Evidence of a G inhibition. In: International symposium on adriamycin. (Carter, S. K., DiMarco, A., Krakoff, I. H., and Mathe, G., eds.), pp. 47–52. New York: Springer 1972
Wilms, K., Wilmanns, W.: Wirkung von Dauno-rubidomycin auf Enzyme der DNA-Synthese in Leukocyten in vivo und in der Kultur. Klin. Wochenschr.50, 866–870 (1972)
Wolff, M., Santiago, H., Duby, M. M.: Delayed distant metastasis from a sacrococcygeal ependymoma. Cancer30, 1046–1067 (1972)
Zimmerman, H. M.: Some contributions of electron microscopy to problems in pathology. Bull. N.Y. Acad. Med.40, 831–862 (1964)
Zimmerman, H. M.: Brain Tumors: their incidence and classification in man and their experimental production. Ann. N. Y. Acad. Sci.159, 337–359 (1969)
Zimmerman, H. M., Arnold, H.: Experimental brain tumors I. Tumors produced with methylcholanthrene. Cancer Res.1, 919–938 (1941)
Zülch, K. J.: The present state of the classification of intracranial tumors and its value for the neurosurgeon. In: The biology and treatment of intracranial tumors. (Fields, W. S. and Sharkey, P. C., eds.), pp. 157–177 (Springfield, IL: Thomas 1962
Zülch, K. J., Wechsler, W.: Pathology and classification of gliomas. Prog. Neurol. Surg,2, pp. 1–84. Basel: Karger 1968
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Slagel, D.E. Methylcholanthrene induced murine primitive neuroectodermal tumor: ultrastructure and nuclear RNA polymerase activity. Acta Neuropathol 44, 173–182 (1978). https://doi.org/10.1007/BF00691064
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DOI: https://doi.org/10.1007/BF00691064