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Nuclear growth and chromatin relaxation-condensation cycle in hepatocytes during the proliferative activation of rat liver

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Virchows Archiv B

Summary

In order to quantify the changes in nucleolar and nuclear volumes and in chromatin condensation produced during proliferative activation we have carried out morphometric studies on hepatocyte nuclei during rat liver regeneration using electron microscopy. To minimize the artefactual effects produced by fixation on subcellular structures we have fixed the livers by perfusion with gluteraldehyde. The mean values for the nucleolar and nuclear volumes were progressively increased until 28 h after 66% partial hepatectomy. The maximum values raised for the nuclei and nucleoli at this time were 3 and 4.28 times, respectively, those of controls. Later, nuclear and nucleolar volumes progressively declined. Two waves of diminution in nuclear electron-dense material were produced after hepatectomy. The first occurred between 0 and 12 h, with minimum values 1.34 times lower than those from control animals at 8 h. The second occurred between 12 and 28 h, with minimum values 2.56 times lower than those from control rats at 24 h. These two waves in chromatin relaxation correlate very well with the transcriptional changes described by other authors during the pre-replicative, replicative and mitotic phases of liver regeneration.

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References

  • Abercrombie M (1946) Stimation of nuclear population from microtomic sections. Anat Rec 94:239–247

    Article  Google Scholar 

  • Bade EG (1967) Biological and ultrastructural aspects of early stages in liver regeneration. In: Their H, Rytoma T (eds) Control of cellular growth in adult organisms. Academic Press, New York, pp 260–269

    Google Scholar 

  • Bader G (1969) Elektronmikroskopische Untersuchungen zur funktioneilen Morphologie der regenierenden Liberzelle nach partieller Hepatektomie. Acta Hepatol-Splenol 16:281–297

    CAS  Google Scholar 

  • Becker FF (1969) Cell division in normal mammalian tissues. Ann Rev Med 20:243–258

    Article  PubMed  CAS  Google Scholar 

  • Becker FF (1970) Normal hepatocyte in division: Regeneration of mammalian liver. Progr Liver Dis 3:60–76

    PubMed  CAS  Google Scholar 

  • Becker FF, Lane BP (1965) Regeneration of mammalian liver. I. Autophagocytosis during dedifferentiation of the liver cell in preparation from cell division. Am J Pathol 47:782–801

    Google Scholar 

  • Becker FF, Lane BP (1966) Regeneration of mammalian liver. IV. Evidence of role of cytoplasmic alterations in preparation for mitosis. Am J Pathol 49:227–235

    PubMed  CAS  Google Scholar 

  • Becker FF, Lane BP (1968) Regeneration of mammalian liver. VI. Retention of phenobarbital-induced cytoplasmic alterations in dividing hepatocytes. Am J Pathol 52:211–225

    PubMed  CAS  Google Scholar 

  • Briane D, Jalozot R, Gontcharoff M (1978) Variation du taux d’euchromatine au cours de la regeneration du foi du rat. Biologie Cellulaire 31:1–6

    Google Scholar 

  • Brues AM, Drury DR, Brues MC (1936) Quantitative study of cell growth in regenerating liver. Arch Pathol (Chicago) 22:658–673

    CAS  Google Scholar 

  • Bucher NLR (1963) Regeneration of mammalian liver. Int Rev Cytol 15:245–300

    Article  PubMed  CAS  Google Scholar 

  • Bucher NLR, Swaffield MN (1964) The rate of incorporation of labeled thymidine into deoxyribonucleic acid of regenerating rat liver in relation to the amount of liver excised. Cancer Res 24:1611–1625

    PubMed  CAS  Google Scholar 

  • Bucher NLR, Malt RA (1971) Regeneration of liver and kidney. In: Ingelfinger FJ (ed) New England J Med medical progress series. Little Brown and Company, Boston, pp 28–43

    Google Scholar 

  • Busch H, Smetana K (1970) The nucleolus. Academic Press, New York, pp 75–82

    Google Scholar 

  • Chaudhuri S, Lieberman I (1968) Control of ribosome synthesis in normal and regenerating liver. J Biol Chem 243:29–33

    PubMed  CAS  Google Scholar 

  • Dabeva D, Dudov P (1982) Transcriptional control of ribosome production in regeneration rat liver. Biochem J 208:101–108

    PubMed  CAS  Google Scholar 

  • Darzynkiewicz Z, Traganos F, Melamed MR (1980) New cell cicle compartments identified by multiparameter flow citometry. Cytochemistry 2:98–108

    Google Scholar 

  • Derenzini M, Lorenzini E, Marinozzi V, Barotti P (1977) Ultrastructural cytochemistry of active chromatin in regeneratin rat hepatocytes. J Ultrastr Res 59:250–262

    Article  CAS  Google Scholar 

  • Derenzini M, Pession-Brizzi A, Novello F (1980) Chromatin condensation in isolated rat hepatocyte nuclei by ribonuclease treatment. Experientia 36:181–183

    Article  PubMed  CAS  Google Scholar 

  • Derenzini M, Pession-Brizzi A, Betts-Eusebi C, Novello F (1981) Relationship between the fine structural organization of chromatin and nucleic acid synthesis in regenerating rat hepatocytes. J Ultrastr Res 75:229–242

    Article  CAS  Google Scholar 

  • Dudov P, Dabeva D (1983) Post-transcriptional regulation of ribosome formation in the nucleus of regenerating rat liver. Biochem J 210:183–192

    PubMed  CAS  Google Scholar 

  • Fahimi HD (1967) Perfusion and inmersion fixation of rat liver with glutaraldehyde. Lab Invest 16:736–750

    PubMed  CAS  Google Scholar 

  • Farquhar MG, Palade GE (1965) Cell junctions in amphibian skin. J Cell Biol 26:263–291

    Article  PubMed  CAS  Google Scholar 

  • Fausto N (1984) Messenger RNA in regenerating liver: implications for the understending of regulated growth. Mol Cell Biochem 59:131–147

    Article  PubMed  CAS  Google Scholar 

  • Fausto N (1986) New perspectives on liver regeneration. Hepatology 6:326–327

    Article  PubMed  CAS  Google Scholar 

  • Fawcett DW (1955) Observations on cytology and electron microscopy of hepatic cells. J Nat Cancer Inst 15:1475–1502

    PubMed  CAS  Google Scholar 

  • Fisher ER, Fisher B (1963) Ultrastructural hepatic changes following partial hepatectomy and portacaval shunt in rat. Lab Invest 12:929–942

    PubMed  CAS  Google Scholar 

  • Fujioka M, Koga M, Lieberman J (1963) Metabolism of ribonucleic acid after partial hepatectomy. J Biol Chem 238:3401–3406

    PubMed  CAS  Google Scholar 

  • Fullman RL (1953) Measurement of particle size in opaque bodies. J Metals 5:447–461

    CAS  Google Scholar 

  • Gaub J (1978) Cytophotometric determination of nuclear nonhistone protein in the replicative phase of rat liver regeneration. Exp Cell Res 114:167–174

    Article  PubMed  CAS  Google Scholar 

  • Grisham JW (1962) Morphologyc study of deoxyribonucleic acid synthesis and cell proliferation in regenerating rat liver: Autoradiography with thymidine-3H. Cancer Res 22:842–849

    PubMed  CAS  Google Scholar 

  • Grisham JW, Tillman MS, Nagel AEH, Compagno MD (1975) Ultrastructure of the proliferating hepatocyte: sinusoidal and endoplasmic reticulum. In: Lesch R, Reutter W (eds) Liver regeneration after experymental injury. Stratton Intercontinental Medical Book Corporation, New York, pp 6–25

    Google Scholar 

  • Harris H (1968) Nucleus and cytoplasm (1st ed). Clarendom Press, Oxford

    Google Scholar 

  • Herdson PB, Garvin PJ, Jennings RB (1964) Fine structural changes produced in rat liver by partial starvation. Am J Pathol 45:157–181

    PubMed  CAS  Google Scholar 

  • Higashi K, Matsuhisa Y, Kitao A, Sakamoto Y (1968) Selective suppresion of nucleolar RNA metabolism in absence of protein synthesis. Biochim Biophys Acta 166:388–393

    PubMed  CAS  Google Scholar 

  • Higgins GM, Anderson RM (1931) Experymental pathology of the liver. I. Restoration of the liver of the white rat following partial surgical removal. Arch Pathol 12:186–202

    Google Scholar 

  • Jordan SW (1964) Electron microscopy of hepatic regeneration. Exp Mol Pathol 3:183–200

    Article  Google Scholar 

  • Lane BP, Becker FF (1966) Regeneration of the mammalian liver. II. Surface alterations during dedifferentiation of the liver cell in preparation for cell division. Am J Pathol 48:183–196

    PubMed  CAS  Google Scholar 

  • Leffert HL, Koch KS, Moran T, Rubalcava B (1979) Hormonal control of rat liver regeneration. Gastroenterology 76:1470–1482

    PubMed  CAS  Google Scholar 

  • Lindberg LG, Vorwerk P (1972) Stimation of volumes of ellipsoid bodies in conglomerates through random plane sections. Lab Invst 27:384–386

    CAS  Google Scholar 

  • Lloyd D, Poole RK, Edwards SW (1982) The cell division Cycle. Temporal organitzation and control of cellular growth and reproduction. Academic Press, London New York, pp 143–180

    Google Scholar 

  • Loud AV (1968) A quantitative stereological description of the ultrastructure of normal rat liver parenchymal cells. J Cell Biol 37:27–46

    Article  PubMed  CAS  Google Scholar 

  • Mironescu S, Dragomir C (1967) Nucleolar behavior in regenerating liver of normal and whole-body-irradiated rats. Cancer Res 27:1819–1830

    PubMed  CAS  Google Scholar 

  • Mitchison JM (1973) The biology of the cell cycle. Cambridge University Press, pp 128–159

  • Morin-Coutu MS, Bilodeaw BS, Simpkins H (1977) Structural and compositional changes in rat liver ribosomes following partial hepatectomy. Lab Invest 37:307–313

    PubMed  CAS  Google Scholar 

  • Muramatsu M, Busch H (1965) Studies on nuclear and nucleolar ribonucleic acid of regenerating rat liver. J Biol Chem 240:3960–3966

    PubMed  CAS  Google Scholar 

  • Murray AB, Strecker W, Silz S (1981) Ultrastructural changes in rat hepatocytes after partial hepatectomy and comparison with biochemical results. J Cell Sci 50:433–448

    PubMed  CAS  Google Scholar 

  • Nadal C (1975) Inhibition of rat hepatocyte in multiplication by serum factors. Virchows Arch [Cell Pathol] 18:273–280

    CAS  Google Scholar 

  • Nadal C (1967) Poliploïdie hépatique du rat. III. Etude des nucléoles des cellules hépatiques du rat normal. Exp Cell Res 48:507–517

    Article  Google Scholar 

  • Nadal C, Zajdela F (1967) Polyploidie hépatique du rat. IV. Variations expérimentales du volume nucléolaire des hépatocytes et leurs mécanismes de régulation. Exp Cell Res 48:518–528

    Article  PubMed  CAS  Google Scholar 

  • Ord MG, Stocken LLA (1980) Nuclear-protein changes in the cell cycle: interphase studies with regenerating rat liver. Biochem Soc Trans 8:759–766

    PubMed  CAS  Google Scholar 

  • Prescott DM (1969) Sequential events of cell life cycle. In: Exploitable molecular mechanisms and neoplasia. Williams and Wilkins, Baltimore, pp 359–370

    Google Scholar 

  • Reynolds ES (1963) The use of lead citrate at high pH as an electron opaque stain in electron microscopy. J Cell Biol 17:208–212

    Article  PubMed  CAS  Google Scholar 

  • Rohr HP, Strebel J, Bianchi L (1970) Ultrastructural morphometric study on rat liver cells in the early regenerative phase after partial hepatectomy. Beitr Pathol 141:52–74

    PubMed  CAS  Google Scholar 

  • Serratosa J (1985) Caracterización estructural y ultraestructural de la regeneratión hepática en la rata. Estudio morfométrico. Doct Thesis. Universidad de Barcelona, pp 200–206

  • Steiner JW, Perz ZM, Taichman LB (1966) Cell population dynamics in liver: Review of quantitative morphological techniques applied to study of physiological and pathological growth. Exp Mol Pathol 5:146–181

    Article  PubMed  CAS  Google Scholar 

  • Stenger RJ, Confer DB (1966) Hepatocellular ultrastructure during liver regeneration after subtotal hepatectomy. Exp Mol Pathol 5:455–457

    Article  PubMed  CAS  Google Scholar 

  • Stowell RE (1948) Nucleic acids and cytologic changes in regenerating rat liver. Arch Pathol (Chicago) 46:164–178

    CAS  Google Scholar 

  • Takatsuka Y, Kohno M, Higashi K, Hirano H, Sakamoto Y (1976) Redistribution of chromatin ribosomal cistrons durin liver regeneration. Exp Cell Res 103:191–199

    Article  PubMed  CAS  Google Scholar 

  • Tsukada K, Lieberman I (1964) Metabolism of nuclear ribonucleic acid after partial hepatectomy. J Biol Chem 239:1564–1568

    PubMed  CAS  Google Scholar 

  • Tubo RA, Berezney R (1987) Pre-replicative association of multiple replicative enzyme activities with the nuclear matrix during liver regeneration. J Biol Chem 262:1148–1154

    PubMed  CAS  Google Scholar 

  • Tucker RW, Pardee AB (1982) Prymary cilia and their role in the regulation of DNA replication and mitosis. In: Nicolini MA (ed) Cell growth. Plenum Press, New York and London, pp 365–376

    Google Scholar 

  • Virolainen M (1967) Humoral control mechanism in liver regeneration. Helsinki. Painovalmiste, pp 1–105

    Google Scholar 

  • Weibel ER, Paumgartner D (1978) Integrated stereologycal and biochemical studies on hepatocytic membranes. II. Correction of section thickness effect on volumen surface density stimates. J Cell Biol 584–597

  • Weibel ER, Kistler GS, Scherle WF (1966) Practical Stereological methods for morphometric cytology. J Cell Biol 30:23–38

    Article  PubMed  CAS  Google Scholar 

  • Weibel ER, Staubli W, Gnagi HR, Hess FA (1969) Correlated morphometric and biochemical studies on the liver cell. I. Morphometric model, stereologic methods and normal morphometric data for rat liver. J Cell Biol 42:69–91

    Article  Google Scholar 

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Authors and Affiliations

  1. Departamento de Farmacología y Toxicologia, Centro de Investigatión y Desarrollo del C.S.I.C., C/Jorge Girona Salgado 18-26, E-08034, Barcelona

    Joan Serratosa

  2. Departamento de Biologia Celular y Anatomia Patológica, Facultad de Medicina, Universidad de Barcelona, C/Avda. Diagonal s/n, E-08028, Barcelona, Spain

    Jordi Domingo, Carles Enrich & Oriol Bachs

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  1. Joan Serratosa
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Serratosa, J., Domingo, J., Enrich, C. et al. Nuclear growth and chromatin relaxation-condensation cycle in hepatocytes during the proliferative activation of rat liver. Virchows Archiv B Cell Pathol 55, 57–64 (1988). https://doi.org/10.1007/BF02896560

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  • DOI: https://doi.org/10.1007/BF02896560

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