Summary
Nervous system tumors were induced in the offspring of BD-IX (inbred) and CFE (non-inbred) rats by transplacental administration of ethylnitrosourea. Tumors of the peripheral nervous system (PNS) were obtained in approximately 80% of all animals, and tumors of the central nervous system (CNS) in 16%. Although several peripheral nerves were sites of tumor formation, the trigeminal nerve was the most frequent nerve affected. In male CFE rats, 70% of all PNS tumors affected the trigeminal nerve. The incidence of trigeminal nerve tumors in female BD-IX rats was only 33% of PNS tumors. Light and electron microscopy showed that the PNS tumors are made-up of Schwann cells, and behave like malignant tumors. The tumors began as a proliferation of recognizable Schwann cells, later they lost their basement lamina, destroyed the nerve tissue and invaded neighboring structures, but did not metastasize. Like their human counterparts, they showed “dense” and “loose” areas. In both of these, Schwann cells were recognized as the tumor cells. Trigeminal nerve tumors were transplanted fromin vitro cultured cells or directly from transplanted fresh tumor fragments to isologous rats (BD-IX). Subcutaneous. intraperitoneal and intracerebral transplants were done. The morphology and behavior of the transplanted tumors were similar to the original malignant neurinomas.
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References
Benda, P.: Protéine S-100 et tumeurs cérébrales humaines. Rev. neurol.118, 368–372 (1968).
Benda, P., Someda, K., Messer, J., Sweet, W. H.: Morphological and immunochemical studies of rat glial tumors and clonal strains propagated in culture. J. Neurosurg.34, 310–323 (1971).
Cravioto, H.: The ultrastructure of acoustic nerve tumors. Acta neuropath. (Berl.)12, 116–140 (1969).
Cravioto, H., Goebel, H.: Nerve sheath tumors transplacentally induced by ethylnitrosourea. Proceed. VI Internat. Congr. Neuropath., pp. 560–561. Paris: Masson et Cie. 1970.
Cravioto, H., Goebel, H., Weiss, J., Ransohoff, J.: Experimental induction of nervous system tumors by alkylating agents. Preliminary observations. J. Neuropath. exp. Neurol.30, 121 (1971)
Cravioto, H., Weiss, J. F., Weiss, E. de C., Palekar, L., Ransohoff, J.: Experimental neurinomas induced with nitrosourea derivatives. J. Neuropath. exp. Neurol.31, 204–205 (1972).
Cravioto, H., Palekar, L., Weiss, E. de C., Bennett, K.: Experimental neurinoma in tissue culture. Acta neuropath. (Berl.)21, 154–164 (1972).
Druckrey, H., Ivankovic, S., Preussman, R.: Selektive Erzeugung maligner Tumoren im Gehirn und Rückenmark von Ratten durch N-Methyl-N-nitrosoharnstoff. Z. Krebsforsch.66, 389–408 (1965).
Druckrey, H., Preussman, R., Ivankovic, S., Schmähl, D.: Organotrope carcinogene Wirkungen bei 65 verschiedenen N-Nitroso-Verbindungen an BD-Ratten. Z. Krebsforsch.69, 103–201 (1967).
Georgsson, G., Wessel, W., Thomas, C.: Zur Feinstruktur experimetenteller Nerventumoren. Z. Krebsforsch.72, 12–23 (1969).
Grossi-Paoletti, E., Paoletti, P., Schiffer, D., Fabiani, A.: Experimental brain tumours induced in rats by nitrosourea derivatives. Part 2. Morphological aspects of nitroso-ethylurea tumours obtained by transplacental induction. J. neurol. Sci.11, 573–582 (1970).
Herschman, H. R.: S-100 protein accumulation in developing animals and cell cultures. In: Cellular aspects of neural growth and differentiation, pp. 491–498. D. C. Pease, ed. Berkeley: Univ. of Calif. Press 1971.
Ivankovic, S., Druckrey, H.: Transplacentare Erzeugung maligner Tumoren des Nervensystems. I. Äthyl-nitroso-harnstoff (ÄNH) an BD-IX-Ratten. Z. Krebsforsch.71, 320–360 (1968).
Jänisch, W., Schreiber, D.: Experimentelle Geschwülste des Zentralnervensystems. Jena: G. Fischer 1969.
Kleihues, P., Matsumoto, S., Wechsler, W., Zülch, K. J.: Morphologie und Wachstum der mit Äthylnitrosoharnstoff transplazentar erzeugten Tumoren des Nervensystems. Verh. dtsch. Ges. Path.3, 372–380 (1968).
Koestner, A., Swenberg, J. A., Wechsler, W.: Transplacental production with ethylnitrosourea of neoplasms of the nervous system in Sprague-Dawley rats. Amer. J. Path.63, 37–50 (1971).
Mennel, H. D., Zülch, K. J.: Zur Morphologie transplacentar erzeugter neurogener Tumoren beim Goldhamster. Acta neuropath. (Berl.)21, 194–203 (1972).
Moore, B. W., Cicero, T. J., Perez, J. J., Cowan, W. M.: Levels of two brain specific proteins during degeneration and development. In: Cellular aspects of neural growth and differentiation, pp. 481–489. D. C. Pease, ed. Berkeley: Univ. of Calif. Press 1971.
Pfeiffer, S. E., Kornblith, P. L., Cares, H. L., Seals, J., Levine, L.: S-100 protein in human acoustic neurinomas. Brain Res.41, 187–193 (1972).
Schiffer, D., Fabiani, A., Grossi-Paoletti, E., Paoletti, P.: Experimental brain tumours induced in rats by nitrosourea derivatives. Part 1. Morphological aspects of methylnitrosourea tumors. J. neurol. Sci.11, 559–572 (1970).
Stavrou, D.: Zur vergleichenden Pathologie der Tumoren des Nervensystems. Eine morphologische und enzymhistochemische Studie an spontanen bzw. experimentellen Tumoren des Nervensystems verschiedener Tierspecies sowie vergleichbaren Tumoren des Menschen. Zbl. Vet.-Med. A18, 585–645 (1971).
Stroobandt, G., Brucher, J. M.: Étude de tumeurs nerveuses obtenues par l'administration de méthylnitrosourée au rat. Neurochirurgie14, 515–535 (1968).
Swenberg, J. A., Koestner, A., Wechsler, W.: The induction of tumors of the nervous system with intravenous methylnitrosourea. Lab. Invest.26, 74–85 (1972).
Thomas, C., Sierra, J. L., Kersting, G.: Hirntumoren bei Ratten nach oraler Gabe von N-Nitroso-N-methyl-harnstoff. Naturwissenschaften54, 228–229 (1967).
Thomas, C., Sierra, J. L., Kersting, G.: Neurogene Tumoren bei Ratten nach intraperitonealer Applikation von N-Nitroso-N-methyl-harnstoff. Naturwissenschaften55, 183 (1968).
Wechsler, W., Kleihues, P., Matsumoto, S., Zülch, K. J., Ivankovic, S., Preussman, R., Druckrey, H.: Pathology of experimental neurogenic tumors chemically induced during prenatal and postnatal life. Ann. N.Y. Acad. Sci.159, 360–408 (1969).
Wechsler, W., Pfeiffer, S. E., Swenberg, J. A., Koestner, A.: S-100 protein in tumors of the central and peripheral nervous system of rats induced by nitrosoureas. J. Neuropath. exp. Neurol.31, 203 (1972).
Weiss, J. F., Grossi-Paoletti, E., Paoletti, P., Schiffer, D., Fabiani, A.: Occurrence of desmosterol in tumors of the nervous system induced in the rat by nitrosourea derivatives. Cancer Res.30, 2107–2109 (1970).
Weiss, J. F., Cravioto, H., Weis, E. de C., Palekar, L., Ransohoff, J.: Sterol metabolism in tumors of the trigeminal nerve induced by nitrosourea derivatives. J. Neuropath. exp. Neurol.31, 203–204 (1972).
Weiss, J. F., Cravioto, H., Ransohoff, J.: Desmosterol accumulation during normal and malignant growth of rat central and peripheral nervous system and in tumor cells in culture. 164th National Meeting of American Chemical Society, New York, 1972.
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This work was supported by research grant NS-08376, CA-10887 and contract number PH-43-77-1174, from the National Institutes of Health, USPHS.
We wish to thank Dr. Seung Kim and Mr. Frank Drnovsky for technical assistance and Mrs. Carmen D. Carrodeguas for secretarial help.
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Cravioto, H., Weiss, J.F., Weiss, E.d.C. et al. Biological characteristics of peripheral nerve tumors induced with ethylnitrosourea. Acta Neuropathol 23, 265–280 (1973). https://doi.org/10.1007/BF00687456
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DOI: https://doi.org/10.1007/BF00687456