Neurochemical Research

, Volume 8, Issue 2, pp 193–206 | Cite as

Cytotoxic effects of methylnitrosourea on developing brain

  • Kannosuke Fujimori
  • Momoko Sunouchi
  • Kazuhide Inoue
  • Masahiro Nakadate
  • Akira Takanaka
  • Yoshihito Omori
Original Articles


The effect of methylnitrosourea (MNU) on cerebellar and cerebral DNA, RNA, protein, lysosomal enzymes (acid DNase, RNase, phosphatase, and beta-glucuronidase), and 2′,3′-cyclic nucleotide 3′-phosphohydrolase (2′,3′-CNPase) activities was studied in rats from birth through 12 days of age. Subcutaneous injection of MNU in a dose of 0.625 mmol/kg caused a suppression of increase in weights and content of DNA, RNA, and protein of cerebellum, but no changes in those of the cerebrum or in body weight. Ratios of protein and RNA to DNA were substantially elevated by MNU in the cerebellum but not in the cerebrum.

Acid DNase and acid RNase activities of MNU-treated rats were significantly elevated beyond the increase of these activities in controls in the cerebellum, but no change in these activities by MNU was observed in the cerebrum. A slight elevation in acid phosphatase activity was observed in the cerebellum but not in the cerebrum after MNU pretreatment. Beta-glucuronidase and 2′,3′-CNPase activities were not changed in the cerebellum or in the cerebrum. These results suggest that in the developing brain, especially in the cerebellum at the mitotic stage, MNU caused cell damage and inhibited cell mitosis.


Cytotoxic Effect Phosphatase Activity Cell Damage Acid Phosphatase Subcutaneous Injection 
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  1. 1.
    Alexandrov, W. A. 1969. Transplacental blastomogenic action of N-nitrosomethylurea in rat offspring. Problem of oncology 15:55–61.Google Scholar
  2. 2.
    Allfrey, V. G., andMirsky, A. E. 1952. Some aspects of the deoxyribonuclease activities of animal tissues. J. Gen. Physiol. 36:227–241.Google Scholar
  3. 3.
    Balazs, R., Kovacs, S., Teichgraber, R., Cocks, W. A., andEayrs, J. T. 1968. Biochemical effects of thyroid deficiency on the developing brain. J. Neurochem. 15:1335–1349.Google Scholar
  4. 4.
    Bosch, D. A., Gerrits, P. O., andEbels, E. J. 1972. The cytotoxic effect of ethylnitrosourea and methylnitrosourea on the nervous system of the rat at different stages of development. Z. Krebsforsch 77:308–318.Google Scholar
  5. 5.
    Bosch, D. A., Ipema, A., andEbels, E. J. 1973. Different cytotoxic effects of methyl- and ethylnitrosourea on developing rat tissues and the influence of cycloheximide on cell death. Z. Krebsforsch 79:255–266.Google Scholar
  6. 6.
    Bosch, D. A. 1977. Short and long term effects of methyl-and ethylnitrosourea (MNU & ENU) on the developing nervous system of the rat. Acta Neurol. Scand. 55:106–122.Google Scholar
  7. 7.
    Burton, K. 1956. A study of the colorimetric estimation of deoxyribonucleic acid. Biochem. J. 62:315–323.Google Scholar
  8. 8.
    Druckrey, H., Ivankovic, S., undPreussman, R. 1965. Selektive Erzeugung maligner Tumoren im Gehirn und Rückenmark von Ratten durch N-Methyl-N-nitrosoharnstoff. Z. Krebsforsch. 66:389–408.Google Scholar
  9. 9.
    Druckrey, H., Ivankovic, S., andGimmy, J. 1973. Cancerogene Wirkung von Methyl- und Äthylnitrosoharnstoff (MNH und ÄNH) nach einmaliger intracerebraler bzw. intracarotidaler injektion bei neugeborenen und jungen BD-Ratten. Z. Krebsforsch. 79:282–297.Google Scholar
  10. 10.
    Druckrey, H., Preussman, R., andIvakovic, S. 1969. N-nitroso compounds in organotropic and transplacental carcinogenesis. Ann. N. Y. Acad. Sci. 163:676–696.Google Scholar
  11. 11.
    Garrett, E. R., Goto, S., andStubbins, J. F. 1965. Kinetics of solvolyses of various N-alkyl-N-nitrosoureas in neutral and alkaline solutions. J. Pharm. Sci. 54:119–123.Google Scholar
  12. 12.
    Ittel, M. E., andMandel, P. 1977. Nuclear ribonuclease activities of rat brain during postnatal development. J. Neurochem. 28:1355–1358.Google Scholar
  13. 13.
    Kurihara, T., andTsukada, Y. 1967. The regional and subcellular distribution of 2′-3′-cyclic nucleotide 3′-phosphohydrolase in the central nervous system. J. Neurochem. 14:1167–1174.Google Scholar
  14. 14.
    Kurihara, T., Nussbaum, J. L., andMandel, P. 1970. 2′,3′-cyclic nucleotide 3′-phosphohydrolase in brains of mutant mice with deficient myelination. J. Neurochem. 17:993–997.Google Scholar
  15. 15.
    Lehman, I. R. 1967. Deoxyribonucleases: their relation to deoxyribonucleic acid synthesis. Ann. Rev. Biochem. 36:645–668.Google Scholar
  16. 16.
    Lowry, O. H., Rosebrough, N. J., Farr, A. L., andRandell, R. J. 1951. Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193:265–275.Google Scholar
  17. 17.
    Matthieu, J. M., Quarles, R. H., De F. Webster, H., Hogan, E. L., andBrady, R. O. 1974. Characterization of the fraction obtained from the CNS (central nervous system) of Jimpy mice by a procedure for myelin isolation. J. Neurochem. 23:517–523.Google Scholar
  18. 18.
    McDonald, M. R. 1955. Ribonucleases methods in enzymology. Meth. Enzymol. 2:427–447.Google Scholar
  19. 19.
    McCalla, D. R., Renver, A., andKitar, R. 1968. Inactivation of biologically active N-methyl-N-nitroso compounds in aqueous solution: effect of various conditions of PH and illumination. Canad. J. Biochem. 46:807–811.Google Scholar
  20. 20.
    Mejbaum, W. 1939. Estimation of small amounts of pentose especially in derivatives of adenylic acid. Z. Physiol. Chem. 258:117–120.Google Scholar
  21. 21.
    Mirault, M. E., andScherrer, K. 1972. In vitro processing of Hela cell peribosomes by a nucleolar endoribonuclease. Fed. Eur. Biochem. Soc. Lett. 20:233–238.Google Scholar
  22. 22.
    Rabié, A., Matrat, M. S., Clavel, M. C., Clos, J., andLegrand, J. 1977. Effects of methylazoxymethanol given at different stages of postnatal life on development of the rat brain: Comparison with those of thyroid deficiency. J. Neurobiol. 8:337–354.Google Scholar
  23. 23.
    Robins, E., Hirsch, H. E., andEmmons, S. S. 1968. Glycosidases in the nervous system. J. B. C. 243:4246–4252.Google Scholar
  24. 24.
    Schreiber, D., Jänisch, W., Scholtze, P., andTausch, H. 1968. Experimentelle Tumoren des Zentralnervensystems. Naturwissenschaft 55:495.Google Scholar
  25. 25.
    Schmidt, G., andThannhauser, S. J. 1945. A method for the determination of deoxyribonucleic acid, ribonucleic acid and phosphoproteins in animal tissues. J. Biol. Chem. 161:83–89.Google Scholar
  26. 26.
    Shirivastaw, K. P. andSubba Rao, K. 1975. Changes in the levels of DNA, RNA, protein and DNases in developing and old chick brain. J. Neurochem. 25:861–865.Google Scholar
  27. 27.
    Sprinkle, T. J., Zaruba, M. E., andMckhann, G. M. 1978. Activity of 2′,3′-cyclic nucleotide 3′-phosphodiesterase in regions of rat brain during development. J. Neurochem. 30:309–314.Google Scholar
  28. 28.
    Subba Rao, K. 1973. Acid deoxyribonuclease activity in developing rat brain. Life Sci. 12:89–96.Google Scholar
  29. 29.
    Sung, S. C. 1971. Thymidine kinase in the developing rat brain. Brain Res., 35:268–271.Google Scholar
  30. 30.
    Swann, P. F. 1968. The rate of breakdown of methyl methanesulphonate, dimethyl sulphonate and N-methyl-N-nitrosourea in the rat. Biochem. J. 110:49–52.Google Scholar
  31. 31.
    Wasterlein, C. G., andPlum, F. 1973. Vulnerability of developing rat brain to electroconvulsive seizures. Arch. Neurol. 29:38–45.Google Scholar

Copyright information

© Plenum Publishing Corporation 1983

Authors and Affiliations

  • Kannosuke Fujimori
    • 1
  • Momoko Sunouchi
    • 1
  • Kazuhide Inoue
    • 1
  • Masahiro Nakadate
    • 2
  • Akira Takanaka
    • 1
  • Yoshihito Omori
    • 1
  1. 1.Division of Pharmacology Biological Safety Research CenterNational Institute of Hygienic SciencesTokyoJapan
  2. 2.Department of Synthetic ChemistryNational Institute of Hygienic SciencesTokyoJapan

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