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Studies on the teratogenic phase specificity of actinomycin D in the rat

  • E. Köhler
  • H. -J. Merker
Article

Summary

In order to elucidate the phase specificity of the embryo-lethal and teratogenic action of actinomycin D (day 5–10 of gestation) rats received 3H-actinomycin D at different times of gestation. The distribution of the radioactivity in the fetus and the placenta was measured. Moreover, the effects of actinomycin D on the RNA polymerase reactions in isolated nuclei of the decidual and fetal tissue were studied. The biochemical results were correlated electron microscopically with specific alterations occurring in different structures of the total implantation sites.

These studies show that the time-dependent embryo-lethal and teratogenic effects of actinomycin D result from a lesion of the embryo and the decidua. The effects of the decidua occur at an earlier time and are more pronounced as compared to those of the embryo. Since the decidua is significant for the nutrition of the embryo till closure of the yolk-sac and beginning of the yolk-sac circulation (day 10 of gestation), the direct effects of actinomycin D on the embryo are intensified by the lesion of the decidua. After day 10 of gestation till the beginning of the placental function 3H-actinomycin D passes over to the embryo. But the concentration-even after a dose of 1 mg/kg-does not suffice to inhibit in vivo RNA polymerase reactions in isolated nuclei.

Key words

Embryonic Development Actinomycin D DNA-dependent RNA Polymerases 

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References

  1. Burton, K.: A study of the conditions and mechanisms of the diphenylamine reaction for the colorimetric estimation of deoxyribonucleic acid. Biochem. J. 62, 315 (1956).Google Scholar
  2. Carpent, G., Desclin, L. M.: A propos du méchanisme d'action de l'actinomycine D sur la gestation chez le rat. R. C. Acad. Sci. (Paris) 264, 2933–2936 (1967).Google Scholar
  3. David, H.: Zum Verhalten von granulärem endoplasmatischem Retikulum, Polysomen und Ribosomen in der Leber nach Actinomycingaben. Verh. anat. Ges. (Jena) 125, 223–227 (1969).Google Scholar
  4. Dingman, C. W., Sporn, M. B.: Actinomycin D and hydrocortisone: intracellular binding in rat liver. Science 149, 1215–1254 (1965).Google Scholar
  5. Flickinger, C. I.: The fine structure of the nucleoli of normal and Actinomycin D-treated Amoeba proteus. J. Ultrastruct. Res. 23, 260–271 (1968).Google Scholar
  6. Goldberg, I. H., Reich, E.: Actinomycin inhibition of RNA synthesis directed by DNA. Fed. Proc. 23, 958–964 (1964).Google Scholar
  7. Goldblatt, P. I., Verbin, R. S., Sullivan, R. I.: Induction of nucleolar segregation by Actinomycin D following inhibition of protein synthesis with cycloheximide. Exp. Cell Res. 63, 117–123 (1970).Google Scholar
  8. Honig, G. R., Rabinowitz, M.: Actinomycin D: Inhibition of protein synthesis unrelated to effect on template RNA synthesis. Science 149, 1504–1506 (1965).Google Scholar
  9. Jordan, R. L., Wilson, J. G.: Radioautographic study of RNA synthesis in normal and Actinomycin D-treated rat embryos. Anat. Rec. 168, 549–564 (1970).Google Scholar
  10. Köhler, E., Merker, H.-J., Ehmke, W., Wojnorowicz, F.: Growth kinetics of mammalian embryos during the stage of differentiation. Naunyn-Schmiedebergs Arch. Pharmakol. 272, 169–181 (1972).Google Scholar
  11. Levinthal, C., Keynan, A., Higa, A.: Messenger RNA turnover and protein synthesis in B. subtilis inhibited by actinomycin D. Proc. nat. Acad. Sci. (Wash.) 48, 1631–1638 (1962).Google Scholar
  12. Merker, H.-J., Villegas, H.: Elmiuntersuchungen zum Problem des Stoffaustausches zwischen Mutter und Keim bei Rattenembryonen des Tages 7–10. Z. Anat. Entwickl.-Gesch. 131, 325–346 (1970).Google Scholar
  13. Reich, E., Goldberg, J. H.: Actinomycin and nucleic acid function. Progr. Nuc. Acid Res. Mol. Biol. 3, 183–234 (1964).Google Scholar
  14. Revel, M., Hiatt, H. H.: The stability of liver messenger RNA. Proc. nat. Acad. Sci. (Wash.) 51, 810–818 (1964).Google Scholar
  15. Skalko, R. G., Morse, J. M. D.: The differential response of the early mouse embryo to actinomycin D treatment in vitro. Teratology 2, 47–54 (1969).Google Scholar
  16. Taska, R. J., Hillman, N.: Effects of Actinomycin D and Cycloheximide on RNA and protein synthesis in cleavage stage mouse embryos. Nature (Lond.) 225, 1022–1025 (1970).Google Scholar
  17. Tata, J. R.: Evidence for two DNA-dependent RNA polymerase activities in isolated rat liver nuclei. Biochim. biophys. Acta (Amst.) 87, 531 (1964).Google Scholar
  18. Tuchmann-Duplessis, H.: The action of anti-tumor drugs on gestation and on embryogenesis. In: Teratology, pp. 75–86. A. Bertelli and L. Donati, ed. Amsterdam: Excerpta Medica Foundation 1969.Google Scholar
  19. —, Mercier-Parot, L.: Sur l'activité tératogène chez le rat de l'actinomycine-D. C. R. Acad. Sci. (Paris) 247, 200 (1958).Google Scholar
  20. ——: Production de diverses malformations par administration d'actinomycine D à la ratte gestante. C.R. Soc. Biol. (Paris) 153, 386–391 (1959a).Google Scholar
  21. ——: A propos de l'action tératogène de l'actinomycine. C.R. Soc. Biol. (Paris) 153, 1697–1700 (1959b).Google Scholar
  22. ——: The teratogenic action of the antibiotic actinomycin D. In: CIBA Foundation Symposium on Congenital Malformations, p. 115. London: J. and A. Churchill (1960a).Google Scholar
  23. ——: A propos de l'action tératogène de l'actinomycine D essais de prévention par l'acide pantothémique. Rev. franç. Etud. clin. biol. 5, 823 (1960b).Google Scholar
  24. Widnell, C. C., Tata, J. R.: Procedure for the isolation of enzymatically active rat liver nuclei. Biochem. J. 92, 313 (1964).Google Scholar
  25. Wilson, J. G.: Effects of acute and chronic treatment with actinomycin D on pregnancy and the fetus in the rat. Harper Hosp. Bull. 24, 109 (1966).Google Scholar

Copyright information

© Springer-Verlag 1972

Authors and Affiliations

  • E. Köhler
    • 1
    • 2
  • H. -J. Merker
    • 1
    • 2
  1. 1.Abt. “Embryonal-Pharmakologie”Pharmak. Institut der Freien Universität BerlinBerlinGermany
  2. 2.Abt. “Embryonal-Pharmakologie”II. Anat. Inst. der Freien Universität BerlinBerlinGermany

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