Acta Neuropathologica

, Volume 49, Issue 2, pp 117–122

Experimental brain tumors by transplacental ENU

Multifactorial study of the latency period
  • D. Schiffer
  • M. T. Giordana
  • A. Mauro
  • G. Racagni
  • F. Bruno
  • S. Pezzotta
  • P. Paoletti
Original Works

Summary

Experimental cerebral tumors have been induced by transplacental ENU. The morphologic study of the brains of treated rats revealed that cellular hyperplasias appear at the 30th day of extrauterine life in the paraventricular white matter, i.e., before the already known “early neoplastic proliferations”. Cytofluorimetric investigations failed to demonstrate differences between treated and control rats during the 1st month. On the contrary, adenylate cyclase activity is very high in that period. The duration of the latency period is discussed.

Key words

ENU tumors Latency period 

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References

  1. Bosch, D. A.: Short and long term effects of methyl- and ethylnitrosourea (MNU and ENU) on the developing nervous system of the rat. I. Long term effects: the induction of (multiple) gliomas. Acta Neurol. Scand.55, 85–105 (1977a)Google Scholar
  2. Bosch, D. A.: Short and long term effects of methyl- and ethylnitrosourea (MNU and ENU) on the developing nervous system of the rat. II. Short term effects: concluding remarks on chemical neuro-oncogenesis. Acta Neurol. Scand.55, 106–122 (1977b)Google Scholar
  3. Daly, J.: Cyclic nucleotides in the nervous system, pp. 64–65, p. 236. New York, London: Plenum Press 1977Google Scholar
  4. Giordana, M. T., Lechner, C., Mauro, A., Pezzotta, S., Soffietti, R., Schiffer, D.: Interval between short and long-term effects of transplacental ENU on rat brain. Proc. Intern. Symp. Multidisciplinary Aspects of brain tumor therapy. Gardone Riviera (Brescia), pp. 349–350. Amsterdam: Elsevier, 1979Google Scholar
  5. Goerttler, K., Arnold, H. P., Michalk, D. V.: Über carcinogeninduzierte diaplacentare Wirkungen bei Ratten. Z. Krebsforsch.74, 396–411 (1970)Google Scholar
  6. Hsie, A. W., Puck, T. T.: Morphological transformation of Chinese hamster cells by dibutyryl adenosine cyclic 3′-5′-monophosphate and testosterone. Proc. Natl. Acad. Sci. USA68, 358–361 (1971)Google Scholar
  7. Kebabian, J. W., Petzold, G. L., Greengard, P.: Dopamine sensitive adenylate cyclase in the caudate nucleus of the rat brain and its similarity to the dopamine receptor. Proc. Natl. Acad. Sci. USA69, 2145–2149 (1972)Google Scholar
  8. Koestner, A., Swenberg, J. A., Wechsler, W.: Transplacental production with ethylnitrosourea of neoplasms of the nervous system in Sprague-Dawley rats. Am. J. Pathol.63, 37–57 (1971)Google Scholar
  9. Laerum, O. D., Rajewsky, M. F.: Neoplastic transformation of fetal rat brain cells in culture after exposure to ethylnitrosourea in vivo. J. Natl. Cancer Inst.55, 1177–1184 (1975)Google Scholar
  10. Laerum, O. D., Hülser, D. F., Rajewsky, M. F.: Electrophysiological properties of ethylnitrosourea-induced, neoplastic neurogenic rat cell lines, cultured in vitro and in vivo. Cancer Res.36, 2153–2161 (1976)Google Scholar
  11. Laerum, O. D., Rajewsky, M. F., Schachner, M., Stavrou, D., Haglid, K. G., Hangen, Å.: Phenotypic properties of neoplastic cell lines developed from fetal rat brain cells in culture after exposure to ethylnitrosourea in vivo. Z. Krebsforsch.89, 273–295 (1977)Google Scholar
  12. Lantos, P. L., Cox, D. J.: The origin of experimental brain tumours: a sequential study. Experientia,32, 1467–1468 (1976)Google Scholar
  13. Lantos, P. L., Pilkington, G. J.: The development of experimental brain tumours. A sequential light and electron microscope study of the subependymal plate. I. Early lesions (Abnormal cell clusters). Acta Neuropathol. (Berl.)45, 167–175 (1979)Google Scholar
  14. Lewis, P. D.: The fate of the subependymal cell in the adult rat brain, with a note on the origin of microglia. Brain91, 721–735 (1968a)Google Scholar
  15. Lewis, P. D.: A quantitative study of cell proliferation in the subependymal layer of the adult rat brain. Exp. Neurol.20, 203–207 (1968b)Google Scholar
  16. Mao, C. C., Guidotti, A.: Simultaneous isolation of cyclic AMP and cyclic GMP in small tissue samples. Anal. Biochem.59, 63–68 (1974)Google Scholar
  17. Nagai, M., Arai, T., Awa, H.: Effect of dibutyryl cyclic AMP on rat tumorgenesis by ethylnitrosourea, p. 664. Abstracts of the VIIIth International Congress of Neuropathology, Washington, 1978Google Scholar
  18. Otten, J., Johnson, G. S., Pastan, I.: Cyclic AMP levels in fibroblasts: relationship to growth rate and contact inhibition of growth. Biochem. Biophys. Res. Commun.44, 1192–1198 (1971)Google Scholar
  19. Paterson, J. A., Privat, A., Ling, E. A., Leblond, C. P.: Investigation of glial cells in semithin sections. III. Transformation of sub-ependymal cells into glial cells, as shown by radioautography after3H-thymidine injection into the lateral ventricle of the brain of young rats. J. Comp. Neurol.149, 83–102 (1973)Google Scholar
  20. Prenna, G., Leiva, S., Mazzini, G.: Determinazione citofluorimetrica del contenuto nucleare di DNA per mezzo della reazione di Feulgen convenzionale. Riv. Istochim. Norm. Patol.17, 332–323 (1971)Google Scholar
  21. Prenna, G., Leiva, S., Mazzini, G.: Quantitation of DNA by cytofluorimetry of the conventional Feulgen reaction. Histochem. J.6, 467–489 (1974a)Google Scholar
  22. Prenna, G., Mazzini, G., Cova, S.: Methodological and instrumentational aspects of cytofluorimetry. Histochem. J.6, 259–278 (1974b)Google Scholar
  23. Racagni, G., Giordana, M. T., Pezzotta, S., Bruno, F., Paoletti, P., Schiffer, D.: Cerebral tumors induced by ENU: changes of adenylate cyclase activity in the tumor latency time. Acta Neurochir. (Wien) (in press) (1979)Google Scholar
  24. Rajewsky, M. F., Goth, R.: Molecular and cellular mechanisms associated with nervous system specific carcinogenesis by ethylnitrosourea. In: Molecular base of malignancy, Deutsch, E., Moser, K., Rainer, H., Stacher, A. (eds.), pp. 2–5. Stuttgart: Thieme (1976)Google Scholar
  25. Ryan, W. L., Heidrick, M. L.: Inhibition of cell growth in vitro by cyclic AMP. Science162, 1484–1485 (1968)Google Scholar
  26. Ryan, W. L., Curtis, G. L.: Chemical carcinogenesis and cyclic AMP. In: Role of cyclic nucleotides in carcinogenesis Gratzner, N., Schultz, J. (eds.). New York: Academic Press 1973Google Scholar
  27. Schiffer, D., Giordana, M. T., Pezzotta, S., Lechner, C., Paoletti, P.: Cerebral tumors by transplacental ENU: a study of the different tumoral stages, particularly of early proliferations. Acta Neuropathol. (Berl.)41, 27–31 (1978)Google Scholar
  28. Sheppard, S. R.: Difference in the cyclic adenosine 3′,5′-monophosphate levels in normal and transformed cells. Nature236, 14–16 (1972)Google Scholar
  29. Yoshida, S., Cravioto, H., Ransohoff, J.: In vitro malignant transformation of fetal brain cells exposed in uterus to ethylnitrosourea, p. 711., Abstracts VIIIth International Congress Neuropathology., Washington 1978Google Scholar

Copyright information

© Springer-Verlag 1980

Authors and Affiliations

  • D. Schiffer
    • 1
  • M. T. Giordana
    • 1
  • A. Mauro
    • 1
  • G. Racagni
    • 2
  • F. Bruno
    • 2
  • S. Pezzotta
    • 3
  • P. Paoletti
    • 3
  1. 1.II. Neurological ClinicUniversity of TurinTurinItaly
  2. 2.Institute of Pharmacology and PharmacognosyUniversity of MilanMilanItaly
  3. 3.Neurosurgical ClinicUniversity of PaviaPaviaItaly

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