Untersuchungen zum cytostatischen Wirkungsmechanismus der Vitamin-A-Säure

  • A. Jung
  • E. Bauer
  • K. Lenger
  • A. Scholz
  • R. Jackisch
Article

Zusammenfassung

Die cytostatischen Effekte der Vitamin-A-Säure auf Ehrlich-Ascites-Tumorzellen in-vitro, sowie auf einige zellfreie Enzymsysteme wurden untersucht. Vitamin-A-Säure beeinflußt konzentrationsabhängig, jedoch unspezifisch die Einbauraten von 14C-Thymidin,-Uridin und -Leucin. Teilweise gereinigte Thymidinkinase aus Ascites-Tumorzellen wird ebensowenig durch Vitamin-A-Säure beeinflußt wie die DNA-Polymerase-Aktivität isolierter Zellkerne. Dagegen lassen sich Einflüsse der Vitamin-A-Säure auf zellfreie Proteinbiosynthese-Systeme, sowie auf die RNA-Polymerasen von Tumorzellkernen nachweisen. Es wird diskutiert, daß für die primären, starken Hemmeffekte auf Ehrlich-Ascites-Tumorzellen in-vitro, die schon bekannten lysosomen-labilisierenden Eigenschaften der Vitamin-A-Säure verantwortlich sind.

Investigations on the cytostatic mechanism of vitamin-A-acid

Summary

The cytostatic effects of vitamin-A-acid on Ehrlich-ascites tumor cells in-vitro and on some cell-free enzyme systems were investigated. In the presence of various vitamin-A-acid concentrations the rates of 14C-thymidine-, -uridine- and -leucine-incorporation were progressively diminished in an unspecific way. Neither partially purified thymidine kinase nor the DNA polymerase activity of isolated nuclei proved to be affected by vitamin-A-acid. In contrast, some influence on the cell-free systems of protein biosynthesis and on the tumor nuclei RNA polymerases could be shown. It is discussed, that the known lysosome-labilizing properties of vitamin-A-acid are responsible for the primary strong inhibitory effects on Ehrlich ascites tumor cells in-vitro.

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Literatur

  1. Bauer,E.: Zum Mechanismus der cytostatischen Wirkung der Vitamin-A-Säure. Biochem. Diplomarbeit, Tübingen (1971)Google Scholar
  2. Bennet,T.P.: Membrane filtration for determining Protein in the presence of interfering substances. Nature (Lond.) 213, 1131–1132 (1967)Google Scholar
  3. Bollag,W.: Vitamin-A-Säure in der Tumortherapie. Tierexperimentelle Untersuchungen über die Wirkung von Vitamin-A-Säure auf Tumoren. Schweiz. med. Wschr. 101, 11–17 (1971)Google Scholar
  4. Bollag,W. (a): Prophylaxis of chemically induced papillomas and carcinomas of mouse skin by vitamin-A-acid. Experientia (Basel) 28, 1219–1220 (1972)Google Scholar
  5. Bollag,W. (b): Prophylaxis of chemically induced benign and malignant epithelial tumors by vitamin-A-acid. Europ. J. Cancer 8, 689–693 (1972)Google Scholar
  6. Brandes,D., Anton,E.: The role of lysosomes in cellular lytic processes. III. Electron histochemical changes in mammary tumors after treatment with cytoxan and vitamin A. Lab. Invest. 15, 987–1006 (1966)Google Scholar
  7. Brandes,D., Anton,E., Schofield,B., Barnard,S.: Role of lysosomal labilizers in treatment of mammary gland carcinomas with cyclophosphamide. Cancer Chemother. Rep. 50, 47–53 (1966)Google Scholar
  8. Brega,A., Falaschi,A., de Carli,L., Pavan,M.: Studies on the mechanism of action of pederine. J. Cell Biol. 36, 485–496 (1968)Google Scholar
  9. Burton,K.: A study of the conditions and mechanism of the diphenylamine reaction for the colorimetric estimation of deoxyribonucleic acid. Biochem. J. 62, 315–323 (1956)Google Scholar
  10. Cohen,M.H., Carbone,P.P.: Enhancement of the antitumor effects of BCNU and cyclophosphamide by vitamin A. J. nat. Cancer Inst. 48, 921–926 (1972)Google Scholar
  11. Dingle,J.T.: Action of vitamin A on the stability of lysosomes in vivo and in vitro. In: de Renck,A.V.S., Cameron,M.P. (Eds.): Lysosomes. Ciba Foundation Symposium, pp 384–398. Boston: Little Brown and Co. (1963)Google Scholar
  12. Karzel,K., Schmid,I.: Über einige biologische Eigenschaften eines permanent in vitro wachsenden Stammes von Ehrlich-Ascites-Tumorzellen. Arzneimittel-Forsch. 18, 1500–1504 (1968)Google Scholar
  13. Leutskaya,Z.K., Fais,D.: The presence of vitamin A in animal cell ribosomes. Biochim. biophysica Acta (Amst.) 312, 103–110 (1973)Google Scholar
  14. Levinson,S. S., Wolf,G.: The effect of vitamin-A-acid on glycoprotein synthesis in skin tumors (Keratoacanthomas). Cancer Res. 32, 2248–2252 (1972)Google Scholar
  15. Lowry,O.H., Rosebrough,N.J., Farr,A.L., Randall,R.J.: Protein measurement with the Folin phenol reagent. J. biol. Chem. 193, 265–275 (1951)Google Scholar
  16. Noll,H.: Polysemes: Analysis of structure and function. In: Campbell,P.N., Sargent,J.K., (Eds.): Techniques in protein biosynthesis. London-New York: Academic Press Vol. 2, 101–179 (1969)Google Scholar
  17. Peterson,N.A., Raghopathy,E., McKean,C.M.: Inhibition by homogentisic acid of polypeptide synthesis in rat liver and brain ribosomal systems. Biochim. biophys. Acta (Amst.) 228, 268–281 (1971)Google Scholar
  18. Probst,H., Ullrich,A., Krauss,G.: Newly synthesized mammalian cell DNA: studies on the reason for the increased affinity to nitrocellulose. Biochim. biophys. Acta (Amst.) 254, 15–29 (1971)Google Scholar
  19. Prutkin,L.: The effect of vitamin A acid on tumorigenesis and protein production. Cancer Res. 28, 1021–1030 (1968)Google Scholar
  20. Prutkin,L., Bogart,B.: The uptake of labeled vitamin A acid in keratoacanthoma. J. Invest. Derm. 55, 249–255 (1970)Google Scholar
  21. Prutkin,L. (a): The effect of actinomycin D on the incorporation of labeled vitamin A acid in normal and tumor epithelium. J. Invest. Derm. 57, 323–329 (1971)Google Scholar
  22. Prutkin,L. (b): Modification of the effect of vitamin-A-acid on the skin tumor keratoacanthoma by applications of actinomycin D. Cancer Res. 31, 1080–1086 (1971)Google Scholar
  23. Prutkin,L.: Antitumor activity of vitamin-A-acid and fluorouracil used in combination on the skin tumor, keratoacanthoma. Cancer Res. 33, 128–133 (1973)Google Scholar
  24. Roeder,R.G., Rutter,W.J.: Specific nucleolar and nucleoplasmic RNA-polymerases. Proc. nat. Acad. Sci. (Wash.) 65, 675–682 (1970)Google Scholar
  25. Roth,J.S.: The phosphorylation of thymidine as a factor controlling cellular proliferation. In: Bianchi,C.P., Hilf,R. (Eds): Protein metabolism and biological function, p. 141–219. Rutgers University press, New Brunswick, New Jersey (1970)Google Scholar
  26. Schindler,R., Day,M., Fischer,G.A.: Culture of neoplastic mast cells and their synthesis of 5-hydroxytryptamine and histamine in vitro. Cancer Res. 19, 47–51 (1959)Google Scholar
  27. Schmähl,D., Krüger,C., Preissler,P.: Versuche zur Krebsprophylaxe mit Vitamin A. Arzneimittel-Forsch. 22, 946–949 (1972)Google Scholar
  28. Stirpe,F., La Placa,M.: Thymidine kinase of rat liver. Biochem. J. 122, 347–351 (1971)Google Scholar
  29. Weissmann,S.M., Smellie,R.M.S., Paul,J.: Studies on the biosynthesis of DNA by extracts of mammalian cells. IV. The phosphorylation of thymidine. Biochim. biophys. Acta (Amst.) 45, 101–110 (1960)Google Scholar
  30. Weitzel,G., Schneider,F., Fretzdorff,A.M., Durst,J., Hirschmann,W.D.: Untersuchungen zum cytostatischen Wirkungsmechanismus der Methylhydrazine. II. Hoppe Seylers Z. physiol. Chem. 348, 433–442 (1967)Google Scholar
  31. Widnell,C.C., Tata,J.R.: A procedure for the isolation of enzymatically active rat-liver nuclei. Biochem. J. 92, 313–317 (1964)Google Scholar

Copyright information

© Springer-Verlag 1974

Authors and Affiliations

  • A. Jung
    • 1
  • E. Bauer
    • 1
  • K. Lenger
    • 1
  • A. Scholz
    • 1
  • R. Jackisch
    • 1
  1. 1.Physiologisch-Chemisches Institut der UniversitätTübingen

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