Summary
Rats were given cytidine-3H and 10 min later 50 mg fluorouracil. They were killed after 25 hours. Actinomycin D was given at various times before sacrifice. The collapse of the nucleolus and the segregation of its components, seen in rats sacrificed one hour after administration of actinomycin D only, was prevented by prior treatment with fluorouracil. In rats treated with fluorouracil and given actinomycin 12 or 20 hours prior to death, there was a more or less pronounced collapse of the nucleolus but no typical segregation of its components. Radioautographs of livers from untreated rats or rats given actinomycin only at the times mentioned, and killed 25 hours after administration of cytidine-3H, were labelled mainly over the cytoplasm. Radioautographs from rats, treated with fluorouracil only, or fluorouracil plus actinomycin, showed labelling over the nucleoli, but depressed labelling over the cytoplasm. Biochemical analysis of RNA labelling showed high ribosomal peaks in untreated rats and rats treated with actinomycin only. Rats treated with fluorouracil, or fluorouracil plus actinomycin showed no labelling of the 29S and 18S ribosomal peaks. The results indicate that fluorouracil blocks or delays the formation of ribosomal RNA and that the inhibition, at least in part, takes place in the nucleolus.
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References
Bernhard, W., C. Frayssinet, C. Lafarge, et E. LeBreton: Lésions nucléolaires précoces provoquées par l'aflatoxine dans les cellules hépatiques. C. R. Acad. Sci. (Paris) 261, 1785–1788 (1965).
—, and N. Granboulan: Electron microscopy of the nucleolus in vertebrate cells. In: A. Dalton and F. Haguenau, Ultrastructure in biological systems, vol. 3, p. 81–149. New York and London: Academic Press 1968.
Chaudhuri, N. K., B. J. Montag, and C. Heidelberger: Studies on fluorinated pyrimidines. III. The metabolism of 5-fIuorouracil-2-C14 and 5-fluoroorotic-2-C14 acid in vivo. Cancer Res. 18, 318–328 (1958).
Heidelberger, C.: Fluorinated pyrimidines. In: J. N. Davidson and W. Cohn, Progress nucleic acid research and molecular biology, vol. 4, p. 1–50. London and New York: Academic Press 1965.
Leblond, C. P., and M. Amano: Symposium: Synthetic processes in the cell nucleus. IV. Synthetic activity in the nucleolus as compared to that in the rest of the cell. J. Histochem. Cytochem. 10, 162–174 (1962).
Narayan, S. K., W. J. Steele, and H. Busch: Evidence that the granular and fibrillar components of nucleoli contain 28 and 6S RNA, respectively. Exp. Cell Res. 43, 483–492 (1966).
Oehlert, W.: Autoradiographische Untersuchungen zur Ribonukleinsäure-Synthese in den verschiedenen Strukturen der Zelle. Beitr. path. Anat. 124, 311–350 (1961).
Perry, R.: The nucleolus and the synthesis of ribosomes. In: J. N. Davidson and W. Cohn, Progress nucleic acid research and molecular biology, vol. 6, 219–257. London and New York: Academic Press 1967.
Simard, R., et W. Bernhard: Le phénomène de la ségrégation nucléolaire: spécificité d'action de certains antimétabolites. Int. J. Cancer 1, 463–479 (1966).
Smuckler, E., and E. Benditt: The early effects of actinomycin on rat liver. Lab. Invest. 14, 1699–1709 (1965).
Stenram, U.: Nucleolar size in the liver of rats fed on high and nonprotein diets after starvation. Acta anat. (Basel) 26, 350–359 (1956).
—: Radioautographic studies with methionine-3H and cytidine-3H in protein-fed, protein-deprived and starved rats. Z. Zellforsch. 58, 107–124 (1962).
—: Cytological, radioautographic and ultrastructural studies on the effect of 5-fluorouracil on rat liver. Z. Zellforsch. 71, 207–216 (1966).
—, and R. Willén: The effect of actinomycin D on ultrastructure and radioautographic ribonucleic acid and protein labeling in rat liver after partial hepatectomy. Cancer Res. 26, 765–772 (1966).
—: Radioautographic, ultrastructural and biochemical studies on the effect of fluorouracil on the RNA synthesis in the liver of rats. Z. Zellforsch. 82, 270–281 (1967).
- Labelling of ribosomal RNA peaks in the liver of rats after administration of tritiated fluorouracil. Experientia (Basel) in press (1968).
Suter, E. R., et J. C. Salomon: Effect de l'actinomycine D sur la structure fine du nucléole des hépatocytes de rats intoxiqués par la thioacétamide. Exp. Cell Res. 43, 248–251 (1966).
Unuma, T., and H. Busch: Formation of microspherules in nucleoli of tumor cells treated with high doses of actinomycin D. Cancer Res. 27, 1232–1242 (1967).
Willén, R., and U. Stenram: RNA synthesis in the liver of rats treated with 5-fluorouracil. Arch. Biochem. 119, 501–503 (1967).
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This work was supported by grants from the Swedish Medical Research Council (Project K68-12X-623-04), the Swedish Cancer Society (Project 68∶31), the Medical Faculty of Uppsala and the Swedish Society for Medical Research.
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Stenram, U., Willén, R. The effect of actinomycin D on RNA synthesis and nucleolar ultrastructure in the liver of rats treated with fluorouracil. Zeitschrift für Zellforschung 90, 403–413 (1968). https://doi.org/10.1007/BF00341995
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DOI: https://doi.org/10.1007/BF00341995