Skip to main content
PMC home page
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1968 Feb 1;36(2):313–328. doi: 10.1083/jcb.36.2.313

THE DISORGANIZATION OF HEPATIC CELL NUCLEOLI INDUCED BY ETHIONINE AND ITS REVERSAL BY ADENINE

Hisashi Shinozuka 1, Peter J Goldblatt 1, Emmanuel Farber 1
PMCID: PMC2107361  PMID: 5638884

Abstract

The structure of nuclei and nucleoli of hepatic cells after short-term ethionine administration was investigated with the electron microscope. By 1½ hr after the injection, a distinct alteration occurred in the nucleoli which was characterized by the appearance of electron-opaque masses in the nucleolonema. After 6–8 hr, the nucleoli showed partial fragmentation into small, dense masses. Large aggregates of interchromatinic granules appeared in the nucleoplasm. Condensation of chromatin became prominent in the nucleoplasm particularly along the nuclear membrane. By 12 hr almost complete fragmentation of nucleoli had occurred. The administration of adenine or methionine at 4 hr prevented the development of nucleolar changes. Also, adenine administration at 8 hr after ethionine completely reversed the nucleolar lesion by 12 hr. After methionine administration at 8 hr, many nucleoli showed incomplete reconstruction with many twisted ropelike structures when viewed 4 hr later. Identical structures were found when adenine was given at 8 hr, and animals were sacrificed 2 hr later. On the basis of this observation, the simplified structures of nucleoli found 2 hr after adenine or 4 hr after methionine appeared to be precursors of the nucleolonema. It is suggested that nucleoli show at least two basic reaction patterns to inhibitors of RNA synthesis, one typified by actinomycin D and one by ethionine.

Full Text

The Full Text of this article is available as a PDF (1.9 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BAGLIO C. M., FARBER E. CORRESPONDENCE BETWEEN RIBOSOME AGGREGATION PATTERNS IN RAT LIVER HOMOGENATES AND IN ELECTRON MICROGRAPHS FOLLOWING ADMINISTRATION OF ETHIONINE. J Mol Biol. 1965 Jun;12:466–467. doi: 10.1016/s0022-2836(65)80269-8. [DOI] [PubMed] [Google Scholar]
  2. BARTELS H., HOHORST H. J. [On the effect of ethionine on the metabolite status of the rat liver]. Biochim Biophys Acta. 1963 Apr 2;71:214–216. doi: 10.1016/0006-3002(63)91011-4. [DOI] [PubMed] [Google Scholar]
  3. Bernhard W., Frayssinet C., Lafarge C., Le Breton E. Lésions nucléolaires précoces provoquées par l'aflatoxine dans les cellules hépatiques du rat. C R Acad Sci Hebd Seances Acad Sci D. 1965 Aug 18;261(7):1785–1788. [PubMed] [Google Scholar]
  4. Bruni C., Porter K. R. The Fine Structure of the Parenchymal Cell of the Normal Rat Liver: I. General Observations. Am J Pathol. 1965 May;46(5):691–755. [PMC free article] [PubMed] [Google Scholar]
  5. FARBER E. ETHIONINE CARCINOGENESIS. Adv Cancer Res. 1963;7:383–474. doi: 10.1016/s0065-230x(08)60986-0. [DOI] [PubMed] [Google Scholar]
  6. Farber E., Shull K. H., McConomy J. M., Castillo A. E. The effects of inosine and aminoimidazole carboxamide upon the ethionine fatty liver. Biochem Pharmacol. 1965 May;14(5):761–767. doi: 10.1016/0006-2952(65)90094-8. [DOI] [PubMed] [Google Scholar]
  7. Heine U., Langlois A. J., Beard J. W. Ultrastructural alterations in avian leukemia myeloblasts exposed to actinomycin D in vitro. Cancer Res. 1966 Sep;26(9):1847–1858. [PubMed] [Google Scholar]
  8. JACOB J., SIRLIN J. L. ELECTRON MICROSCOPE STUDIES ON SALIVARY GLAND CELLS. IV. THE NUCLEUS OF SMITTIA PARTHENOGENETICA (CHIRONOMIDAE) WITH SPECIAL REFERENCE TO THE NUCLEOLUS AND THE EFFECTS OF ACTINOMYCIN THEREON. J Ultrastruct Res. 1964 Oct;11:315–328. doi: 10.1016/s0022-5320(64)90036-x. [DOI] [PubMed] [Google Scholar]
  9. JOURNEY L. J., GOLDSTEIN M. N. Electron microscope studies on HeLa cell lines sensitive and resistant to actinomycin D. Cancer Res. 1961 Aug;21:929–932. [PubMed] [Google Scholar]
  10. KARNOVSKY M. J. Simple methods for "staining with lead" at high pH in electron microscopy. J Biophys Biochem Cytol. 1961 Dec;11:729–732. doi: 10.1083/jcb.11.3.729. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. LAPIS K., BERNHARD W. THE EFFECT OF MITOMYCIN-C ON THE NUCLEOLAR FINE STRUCTURE OF KB CELLS IN CELL CULTURE. Cancer Res. 1965 Jun;25:628–645. [PubMed] [Google Scholar]
  12. LUFT J. H. Improvements in epoxy resin embedding methods. J Biophys Biochem Cytol. 1961 Feb;9:409–414. doi: 10.1083/jcb.9.2.409. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Lazarus S. S., Vethamany V. G., Shapiro S. H., Amsterdam D. Histochemistry and fine structure of 4-nitroquinoline-N-oxide-induced nuclear inclusions. Cancer Res. 1966 Nov;26(11):2229–2238. [PubMed] [Google Scholar]
  14. Miyai K., Steiner J. W. Fine structure of interphase liver cell nuclei in acute ethionine intoxication. Lab Invest. 1967 May;16(5):677–692. [PubMed] [Google Scholar]
  15. Miyai K., Steiner J. W. Fine structure of interphase liver cell nuclei in subacute ethionine intoxication. Exp Mol Pathol. 1965 Oct;4(5):525–566. doi: 10.1016/0014-4800(65)90016-x. [DOI] [PubMed] [Google Scholar]
  16. REYNOLDS R. C., MONTGOMERY P. O., HUGHES B. NUCLEOLAR "CAPS" PRODUCED BY ACTINOMYCIN D. Cancer Res. 1964 Aug;24:1269–1277. [PubMed] [Google Scholar]
  17. REYNOLDS R. C., MONTGOMERY P. O., KARNEY D. H. Nucleolars "caps'--a morphologic entity produced by the carcinogen 4-nitroquinoline N-oxide. Cancer Res. 1963 May;23:535–538. [PubMed] [Google Scholar]
  18. SCHOEFL G. I. THE EFFECT OF ACTINOMYCIN D ON THE FINE STRUCTURE OF THE NUCLEOLUS. J Ultrastruct Res. 1964 Apr;10:224–243. doi: 10.1016/s0022-5320(64)80007-1. [DOI] [PubMed] [Google Scholar]
  19. SHULL K. H. Hepatic phosphorylase and adenosine triphosphate levels in ethionine-treated rats. J Biol Chem. 1962 May;237:1734–1735. [PubMed] [Google Scholar]
  20. STEKOL J. A. BIOCHEMICAL BASIS FOR ETHIONINE EFFECTS ON TISSUES. Adv Enzymol Relat Areas Mol Biol. 1963;25:369–393. doi: 10.1002/9780470122709.ch7. [DOI] [PubMed] [Google Scholar]
  21. STEVENS B. J. THE EFFECT OF ACTINOMYCIN D ON NUCLEOLAR AND NUCLEAR FINE STRUCTURE IN THE SALIVARY GLAND CELL OF HIRONOMUS THUMMI. J Ultrastruct Res. 1964 Oct;11:329–353. doi: 10.1016/s0022-5320(64)90037-1. [DOI] [PubMed] [Google Scholar]
  22. Shull K. H., McConomy J., Vogt M., Castillo A., Farber E. On the mechanism of induction of hepatic adenosine triphosphate deficiency by ethionine. J Biol Chem. 1966 Nov 10;241(21):5060–5070. [PubMed] [Google Scholar]
  23. Simard R., Bernhard W. Le phénomène de la ségrégation nucléolaire: spécificité d'action de certains antimétabolites. Int J Cancer. 1966 Sep 15;1(5):463–479. doi: 10.1002/ijc.2910010506. [DOI] [PubMed] [Google Scholar]
  24. Simard R. Specific nuclear and nucleolar ultrastructural lesions induced by proflavin and similarly acting antimetabolites in tissue culture. Cancer Res. 1966 Nov;26(11):2316–2328. [PubMed] [Google Scholar]
  25. Svoboda D., Grady H. J., Higginson J. Aflatoxin B1 injury in rat and monkey liver. Am J Pathol. 1966 Dec;49(6):1023–1051. [PMC free article] [PubMed] [Google Scholar]
  26. Trump B. F., Goldblatt P. J., Stowell R. E. Studies of mouse liver necrosis in vitro. Ultrastructural and cytochemical alterations in hepatic parenchymal cell nuclei. Lab Invest. 1965 Nov;14(11):1969–1999. [PubMed] [Google Scholar]
  27. VILLA-TREVINO S., FARBER E., STAEHELIN T., WETTSTEIN F. O., NOLL H. BREAKDOWN AND REASSEMBLY OF RAT LIVER ERGOSOMES AFTER ADMINISTRATION OF ETHIONINE OR PUROMYCIN. J Biol Chem. 1964 Nov;239:3826–3833. [PubMed] [Google Scholar]
  28. VILLA-TREVINO S., SHULL K. H., FARBER E. The role of adenosine triphosphate deficiency in ethionine-induced inhibition of protein synthesis. J Biol Chem. 1963 May;238:1757–1763. [PubMed] [Google Scholar]
  29. Villa-Trevino S., Shull K. H., Farber E. The inhibition of liver ribonucleic acid synthesis by ethionine. J Biol Chem. 1966 Oct 25;241(20):4670–4674. [PubMed] [Google Scholar]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press

RESOURCES