Summary
The effects of fluorouracil and uracil on the ultrastructure and RNA synthesis in the liver of rats have been studied. High doses of uracil, contrary to fluorouracil, had no effects on nucleolar ultrastructure. Fluorouracil, even in low doses, depressed the RNA synthesis as studied after cytidine-3H administration. In the radioautographs the depression was especially seen to affect the cytoplasmic labelling. The biochemical analysis showed signs of a depression of ribosomal RNA synthesis and a block or delay in the maturation of ribosomal RNA. Repeated, high doses of uracil also depressed the RNA synthesis but there did not seem to be any delay in the maturation of ribosomal RNA. The results suggest that fluorouracil may affect the RNA metabolism in the nucleoli.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Andoh, T., andE. Chargaff: Formation and fate of abnormal ribosomes of E. coli cells treated with 5-fluorouracil, Proc. nat. Acad. Sci. (Wash.)54, 1181–1189 (1965).
Aronson, A.: The effect of 5-fluorouracil on bacterial protein and ribonucleic acid synthesis. Biochim. biophys. Acta (Amst.)49, 98–107 (1961).
Chaudhuri, N. K., B. J. Montag, andC. Heidelberger: Studies on fluorinated pyrimidines. III. The metabolism of 5-fluorouracil-2-C14 and 5-fluorcorotic-2-C14 acid in vivo. Cancer Res.18, 318–328 (1958).
Comb, D., andN. Sarkar: The binding of 5 S ribosomal ribonucleic acid to ribosomal subunits. J. molec. Biol.25, 317–330 (1967).
Dessev, G. N., G. G. Markov, andR. G. Tsanev: Localization of the DNA-like RNA in rat liver cytoplasm. C. R. Acad. Bulg. Sci.19, 755–758 (1966).
Georgiev, G. P.: The nucleolus and ribosomal RNA synthesis in mammalian cells. Monographs Natl. Cancer Inst.23, 513–525 (1966).
Heidelberger, C.: Fluorinated pyrimidines. In:J. N. Davidson andW. Cohn, Progress in nucleic acid research and molecular biology, vol 4, p. 1–50. London and New York: Academic Press 1965.
Henshaw, E. C., M. Revel, andH. H. Hiatt: A cytoplasmic particle bearing messenger ribonucleic acid in rat liver. J. molec. Biol.14, 241–256 (1965).
Higgnett, R. C.: Interference of 5-fluorouracil in the biosynthesis of ribosomes in Staphylococcus aureus (strain Duncan). Biochim. biophys. Acta (Amst.)114, 559–564 (1966).
Iwabuchi, M., E. Otaka, M. Kono, andS. Osawa: The effect of 5-fluorouracil on the ribosome formation in Escherichia coli. Biochim. biophys. Acta (Amst.)114, 83–94 (1966).
Kempner, E.: The selection and utilization of metabolic analogs for nucleic acid synthesis. Biochim. biophys. Acta (Amst.)53, 111–122 (1961).
Kloet, S. R. de, andP. J. Strijkert: Selective inhibition of ribosomal RNA synthesis in Saccharomyces carlsbergiensis by 5-fluorouracil. Biochem. biophys. Res. Commun.23, 49–55 (1966).
Kono, M., andS. Osawa: Intermediary steps of ribosome formation in Escherichia coli. Biochim. biophys. Acta (Amst.)87, 326–334 (1964).
Lapis, K., andI. Benedeczky: Antimetabolite-induced changes in the fine structure of tumour cells. Acta biol. Acad. Sci. hung.17, 199–215 (1966).
Lerman, M. I., E. A. Vladimirtseva, V. V. Tersikh, andG. P. Georgiev: The nature of newly formed ribonucleic acid of the animal cell. Biochemistry30, 322–332 (1965) [translated from russian].
Lindner, A., T. Kutkam, K. Sankaranarayanan, R. Rucker, andJ. Arradondo: Inhibition of Ehrlich ascites tumor with 5-fluorouracil and other agents. Exp. Cell Res., Suppl.9, 485–508 (1963).
Muramatsu, M., J. Hodnett, andH. Busch: Base composition of fractions of nuclear and nucleolar ribonucleic acid obtained by sedimentation and chromatography. J. biol. Chem.241, 1544–1550 (1966).
Penman, S.: RNA metabolism in the HeLa cell nucleus. J. molec. Biol.17, 117–130 (1966).
Perry, R.: On ribosome biogenesis. Monographs Natl. Cancer Inst.23, 527–545 (1966).
Philips, F.: Personal communication (1965).
Samarina, O. P., A. A. Krichevskaya, andG. P. Georgiev: Nuclear ribonucleoprotein particles containing messenger ribonucleic acid. Nature (Lond.)210, 1319–1322 (1966).
Schwartz, H., andM. Garofalo: Degradation of RNA in liver of rats treated with actinomycin D. Mol. Pharmacol.3, 1–8 (1967).
Sells, B. H., andK. Crudup: Ribosome production during recovery from puromycin treatment: influence of 5-fluorouracil. Biochim. biophys. Acta (Amst.)123, 253–264 (1966).
Shimizu, M.: The appearance of perinucleolar halos in cultured cells with 5-fluorouracil. Acta med. Okayama19, 123–131 (1965).
Simard, R., andW. Bernhard: Le phénomène de la ségrégation nucléolaire: spécificité d'action de certains antimétabolites. Int. J. Cancer1, 463–479 (1966).
Steele, W., andH. Busch: Studies on the ribonucleic acid components of the nucleolar ribonucleoprotein network. Biochim. biophys. Aeta (Amst.)129, 54–67 (1966).
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 RNA and protein labeling and the nucleolar volume in rats following administration of moderate doses of actinomycin D. Exp. Cell Res.36, 242–255 (1964).
—: Electron-microscopic study on liver cells of rats treated with actinomycin D. Z. Zellforsch.65, 211–219 (1965).
—: Cytological, radioautographic and ultrastructural studies on the effect of 5-fluorouracil on rat liver. Z. Zellforsch.71, 207–216 (1966).
—, andR. 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).
—: Electron microscopical observations of inhibitory effect of puromycin on liver regeneration after partial hepatectomy. Exp. Cell Res.46, 457–459 (1967).
Trakatellis, A., A. E. Axelrod, andM. Montjar: Actinomycin D and messenger-RNA turnover. Nature (Lond.)203, 1134–1136 (1964).
Warner, J., R. Soeiro, H. C. Birnblom, M. Girard, andJ. Darnell: Rapidly labeled HeLa cell nuclear RNA. J. molec. Biol.19, 349–361 (1966).
Willén, R., andU. Stenram: RNA synthesis in the liver of rats treated with 5-fluorouracil. Arch. Biochem.119, 501–503 (1967).
Author information
Authors and Affiliations
Additional information
The investigation was supported by grants from the Swedish Medical Research Council (Project K 67–12 X-623-03), the Swedish Cancer Society (Project 67:31) and the Medical Faculty of Uppsala.
Rights and permissions
About this article
Cite this article
Stenram, U., Willén, R. 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). https://doi.org/10.1007/BF01901706
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF01901706