Summary
Brain tumors are regularly induced in rats by chronic intravenous application of methylnitrosourea (5 mg/kg/week). In 66 experimental animals we looked for early histologic and histochemical changes during the genesis of such brain tumors. After a lag period of 225–300 days a total of 60 tumors of the central nervous system developed: 8 gliomas, 33 gliomatous microtumors, 8 sarcomas, 5 sarcomatous microtumors, 6 neurinomas. In addition 15 areas with characteristic histochemical changes, but without cell proliferation were found. In these areas acid mucopolysaccharides could be demonstrated by the iron binding reaction or by alcian blue (alcianophilic areas without cell proliferation). The same histochemical changes were seen in all gliomatous microtumors (alcianophilic areas with cell proliferation) and in fully developed gliomas. The positive staining reaction for acid mucopolysaccharides may be diffuse or weblike. In central regions of larger gliomas alcianophilia tends to disappear. Alcianophilic areas with and without cell proliferation and fully developed gliomas show a very similar localization: they involve preferentially the white matter and regions near the lateral ventricles. We conclude from these observations that gliomas originate from alcianophilic areas rich in acid mucopolysaccharides. The histochemical findings point to an early dysregulation of carbohydrate metabolism during the neoplastic transformation of glial cells. In contrast to gliomas, sarcomas never show an accumulation of acid mucopolysaccharides. This histochemical difference may help to distinguish between gliomas and sarcomas.
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Literatur
Arseni, C., Carp, N., Mestes, E., Adel, M.: Histochemistry of mucopolysaccharides in brain tumors. Acta neuropath. (Berl.)7, 275–284 (1967)
Bannasch, P.: Carcinogen-induced cellular thesaurismoses and neoplastic cell transformation. Rec. Res. Cancer Res., Vol. 44, p. 115–126. Berlin-Heidelberg-New York: Springer 1974
Bannasch, P.: Die Cytologie der Hepatocarcinogenese. In: Handbuch der Allgemeinen Pathologie, VI, 7, p. 123–276. Berlin-Heidelberg-New York, Springer 1975
Dorfman, A., Ho, P. L.: Synthesis of acid mucopolysaccharides by glial tumor cells in tissue culture. Proc. Nat. Acad. Sci. (Wash.)66, 495–499 (1970)
Druckrey, H., Ivankovic, S., Preussmann, R.: Selektive Erzeugung von Hirntumoren bei Ratten durch Methylnitrosoharnstoff. Naturwissenschaften51, 144 (1964)
Druckrey, H., Preussmann, R., Ivankovic, S., Schmähl, D.: Organotrope carcinogene Wirkungen bei 65 verschiedenen N-Nitroso-Verbindungen an BD-Ratten. Z. Krebsforsch.69, 103–201 (1967)
Earle, K. M.: Histochemistry of brain tumors. A study of the PAS-positive substances in 486 intracranial neoplasms and 30 intraspinal neoplasms. Lab. Invest.8, 665–672 (1959)
Engelhardt, A., Bannasch, P.: Histochemischer Nachweis von sauren Mucopolysacchariden im Rattenhirn während der Genese experimenteller Gliome. Verh. Dtsch. Ges. Path.60, 345 (1976)
Fisher, E. R., Lillie, R. D.: The effect of methylation on basophilia. J. Histochem. Cytochem.2, 81–87 (1954)
Gomori, G.: The histochemistry of mucopolysaccharides. Brit. J. exp. Path.35, 377–380 (1954)
Hale, C. W.: Histochemical demonstration of acid polysaccharides in animal tissues. Nature (Lond.)157, 802 (1946)
Hotchkiss, R. D.: A microchemical reaction resulting in the staining of polysaccharide structures in fixed tissue preparations. Arch. Biochem.16, 131–141 (1948)
Lampert, I. A., Lewis, P. D.: Demonstration of acidic polyanions in certain glial cells during postnatal rat brain development. Brain Res.73, 356–361 (1974)
Leppi, T. J., Stoward, P. J.: On the use of testicular hyaluronidase for identifying acid mucins in tissue sections. J. Histochem. Cytochem.13, 406–407 (1965)
Lev, R., Spicer, S. S.: Specific staining of sulphate groups with alcian blue at low pH. J. Histochem. Cytochem.12, 309 (1964)
Margolis, R. U., Margolis, R. K.: Metabolism and functions of glycoproteins and glycosaminoglycans in nervous tissue. Int. J. Biochem.8, 85–91 (1977)
McManus, J. F. A.: Histological demonstration of mucin after periodic acid. Nature (Lond.)158, 202 (1946)
Meller, K.: Modifikation der Silberimprägnation zur Darstellung der Zellen des Oligodendroglioms im Paraffinmaterial. Acta neuropath. (Berl.)2, 497–500 (1963)
Mennel, H. D., Ivankovic, S.: Experimentelle Erzeugung von Tumoren des Nervensystems. In: Handbuch der Allgemeinen Pathologie VI, 7, 33–122. Berlin-Heidelberg-New York: Springer 1975
Mowry, R. W.: The spacial value of methods that color both acid and vicinal hydroxyl groups in the histochemical study of mucins. With revised directions for the colloidal iron stain, the use of alcian blue 8 GX and their combinations with the periodic acid Schiff reaction. Ann. N. Y. Acad. Sci.106, 402–423 (1963)
Müller, G.: Über eine Vereinfachung der Reaktion nach Hale. Acta histochem. (Jena)2, 68–70 (1955)
Pearse, A. G. E.: Histochemistry, Theoretical and Applied, III. Ed., Vol. 1, p. 294–380. Boston: Little, Brown & Co. 1968
Ramadan, M. A., Wechsler, W.: Transplacental induction of neurogenic tumors in BD IX rats by intragastric administration of ethylnitrosourea precursors. Z. Krebsforsch.84, 177–187 (1975)
Rath, F. W., Schneider, H., Van Calker, H.: Histochemische Untersuchungen an Frühstadien experimenteller Hirntumoren. In: Experimentelle Neuroonkologie, hrsg. von D. Schreiber und W. Jänisch. Halle: Johann Ambrosius Barth 1974
Schiffer, D., Fabiani, A.: Contribution of histochemistry to knowledge of brain-tumor metabolism. In: The experimental biology of brain tumors, edit. by W. M. Kirsch, E. Grossi-Paoletti, P. Paoletti. Springfield: Charles C. Thomas 1972
Schiffer, D., Giordana, M. T.: On the occurence and significance of acid mucopolysaccharides in oligodendrogliomas experimentally induced in the rat by nitrosourea derivates. In: Experimentelle Neuroonkologie, hrsg. von D. Schreiber und W. Jänisch. Halle: Johann Ambrosius Barth 1974
Schiffer, D., Giordana, M. T.: Acid mucopolysaccharides in experimental brain tumors. Proc. VII Intern. Congr. Neuropath. Budapest. Vol. I, p. 533–540. Amsterdam: Excerpta Medica 1975
Scott, J. E., Dorling, J.: Differential staining of acid glycosaminoglycans (mucopolysaccharides) by Alcian Blue in salt solutions. Histochemie5, 221–233 (1965)
Smith, B., Butler, M.: Acid mucopolysaccharides in tumors of the myelin sheath cells, the oligodendroglioma and the neurilemmoma. Acta neuropath. (Berl.)23, 181–185 (1973)
Stavrou, D.: Beitrag zur Morphologie und Enzymhistochemie experimenteller Tumoren des Zentralnervensystems der Ratte. I. Morphologische Befunde. Acta neuropath. (Berl.)15, 220–230 (1970a)
Stavrou, D.: Beitrag zur Morphologie und Enzymhistochemie experimenteller Tumoren des Zentralnervensystems der Ratte. II. Enzymhistochemische Befunde. Acta neuropath. (Berl.)15, 231–239 (1970b)
Stavrou, D.: Zur vergleichenden Pathologie der Tumoren des Nervensystems. Zbl. Vet. Med. A18, 585–645 (1971)
Steedman, H. F.: Alcian blue 8 GS, a new stain for mucin. Quar. J. micr. Sci.91, 477–479 (1950)
Stroobandt, G., Brucher, J. M.: Etude de tumeurs nerveuses obtenues par l'administration de méthylnitrosourée au rat. Neurochirurgie14, 515–535 (1968)
Wechsler, W., Kleihues, P., Matsumoto, S., Zülch, K. J., Ivankovic, S., Preussmann, 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.: Carcinogenic and teratogenic effects of ethylnitrosourea and methylnitrosourea during pregnancy in experimental rats. In: Transplacental Carcinogenesis. Lyon: IARC Scientific Publ.4, 127–142 (1973)
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Der Arbeit liegen die Ergebnisse einer Inaugural-Dissertation zugrunde (A. Engelhardt, Heidelberg 1977)
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Engelhardt, A., Bannasch, P. Histochemie saurer Mucopolysaccharide während der Genese Methylnitrosoharnstoff-induzierter Hirntumoren der Ratte. Acta Neuropathol 42, 197–204 (1978). https://doi.org/10.1007/BF00690357
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DOI: https://doi.org/10.1007/BF00690357