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Cell Proliferation and Cell Death in the Liver: Patterns, Mechanisms and Measurements

  • Malcolm Alison
  • Matthew Golding
  • Catherine Sarraf
Conference paper
Part of the NATO ASI Series book series (volume 88)

Abstract

Measurements of cell proliferation and cell death in the liver are important in development, normal cell turnover, wound healing and tumour progression. A large literature exists on the subject of cell proliferation, not least because of the feeling that the rate of growth of any human or animal tumour will reflect its subsequent behaviour pattern, though as persuasively illustrated many years ago by Steel (Steel 1977) this need not be the case. Before addressing the techniques it is necessary to consider the proliferative status of the liver. Figure 1 depicts the cell cycle, and the very low proliferative rate in the normal liver strongly suggests that most hepatocytes are in the Go phase. So any stimulus increasing the proliferative rate does so by triggering cells into the cell cycle rather than by shortening the cell cycle of already cycling cells. In young adults at least, there is no evidence that there are any hepatocytes which have terminally differentiated, which would render their re-entry into the cell cycle impossible (Wright and Alison 1984; Alison 1986).

Keywords

Proliferate Cell Nuclear Antigen Littoral Cell Centrilobular Necrosis Apoptotic Hepatocyte Proliferative Cell Cycle 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Alison MR (1986) Regulation of liver growth. Physiol Rev 66: 499–541PubMedGoogle Scholar
  2. Alison MR, Hully JR (1991) Stimulus dependent phenotypic diversity in the resistant hepatocyte model. In: Columbano A, Feo F, Pascale R, Pani P (eds). Chemical carcinogenesis 2. Modulating factors. New York: Plenum, pp563–577CrossRefGoogle Scholar
  3. Alison MR, Sarraf CE (1992) Apoptosis: - a gene-directed programme of cell death. J R Coll Phys 26: 25–35Google Scholar
  4. Alison MR, Wilkins MJE, Walker SM, Hully JR (1987) Cell population size control in the rat liver: the response of hepatocytes in various proliferative states to a mitogenic stimulus. Epithelia 1: 53–64Google Scholar
  5. Ansari B, Coates PJ, Greenstein BD, Hall PA (1993) In situ end-labelling detects DNA strand breaks in apoptosis and other physiological and pathological states. J Pathol 170: 1–8PubMedCrossRefGoogle Scholar
  6. Arends MJ, Morris RG, Wyllie AH (1990) Apoptosis. The role of the endonuclease. Am J Pathol 136:593–608PubMedGoogle Scholar
  7. Boobis AR, Fawthrop DJ, Davies DS (1992) Mechanisms of cell injury. In: Oxford Textbook of Pathology. Vol 1 (eds JOD McGee, PG Isaacson, NA Wright) Oxford University Press, Oxford. pp181–193Google Scholar
  8. Bursch W, Oberhammer F, Jirtle RL et al (1993) Transforming growth factor-β1 as a signal for induction of cell death by apoptosis. Br J Cancer 67: 531–536PubMedCrossRefGoogle Scholar
  9. Bursch W, Taper HS, Lauer B, Schulte-Hermann R (1985) Quantitative histological and histochemical studies on the occurrence and stages of controlled cell death (apoptosis) during regression of rat liver hyperplasia. Virch Arch [Cell Pathol] 50: 153–166CrossRefGoogle Scholar
  10. Columbano A, Ledda-Columbano GM, Coni PP et al (1985) Occurrence of cell death (apoptosis) during the involution of rat liver hyperplasia. Lab Invest 52: 670–673PubMedGoogle Scholar
  11. Columbano A, Ledda-Columbano GM, Rao PM, Rajalakshmi S, Sarma DSR (1984) Occurrence of cell death (apoptosis) in preneoplastic and neoplastic liver cells. Am J Pathol 116: 441–446PubMedGoogle Scholar
  12. Fabrikant JI (1968) The kinetics of cellular proliferation in the regenerating liver. J Cell Biol 36:551–565PubMedCrossRefGoogle Scholar
  13. Fawthrop DJ, Boobis AR, Davies DS (1991) Mechanisms of cell death. Arch Toxicol 65: 437–444PubMedCrossRefGoogle Scholar
  14. Fesus L, Davies JA, Piacentini M (1991) Apoptosis: molecular mechanisms in programmed cell death. Eur J Cell Biol 56:170–177PubMedGoogle Scholar
  15. Gerbracht U, Bursch W, Kraus P et al (1990) Effects of hypolipidaemic drugs nafenopin and Clofibrate on phenotypic expression and cell death (apoptosis) in altered foci of rat liver. Carcinogenesis 11: 617–624PubMedCrossRefGoogle Scholar
  16. Gerdes J, Becker MHG, Key G (1992) Imunohistological detection of tumour growth fraction (Ki-67 antigen) in formalin fixed and routinely processed tissues. J Pathol 168: 85–86PubMedCrossRefGoogle Scholar
  17. Gerdes J, Schwab U, Lemke H, Stein H (1983) Production of a monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation. Int J Cancer 31:13–20PubMedCrossRefGoogle Scholar
  18. Gratzner HG (1982) Monoclonal antibody to 5-bromo and 5-iododeoxyuridine: a new reagent for detection of DNA replication. Science 218: 474–475PubMedCrossRefGoogle Scholar
  19. Hall PA, Levison DA (1990) Review: Assessment of cell proliferation in histological material. J Clin Path 43:184–191PubMedCrossRefGoogle Scholar
  20. Hall PA, Levison DA, Woods AL, Yu CCW, Kellock DB, Watkins JA, Barnes DM, Gillett CE, Camplejohn R, Dover R, Waseem NH, Lane DP (1990) Proliferating cell nuclear antigen (PCNA) immunolocalization in paraffin sections: an index of cell proliferation with evidence of deregulated expression in some neoplasms. J Pathol 162: 285–294PubMedCrossRefGoogle Scholar
  21. Hall PA, Levison DA, Wright NA (eds) (1992) Assessment of cell proliferation in clinical practice. Springer-Verlag, London UKGoogle Scholar
  22. Hayashi Y, Koike M, Matsutani M, Hoshino T (1988) Effects of fixation time and enzymatic digestion on immunohistochemical demonstration of bromodeoxyuridine in formalin-fixed, paraffin embedded tissue. J Histochem Cytochem 36: 511–514PubMedCrossRefGoogle Scholar
  23. Kerr JFR, Wyllie AH, Currie AR (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 68: 239–257CrossRefGoogle Scholar
  24. Ledda-Columbano GM, Coni P, Curto M et al (1991) Induction of two different modes of cell death, apoptosis and necrosis, in rat liver after a single dose of thioacetamide. Am J Pathol 139: 1099–1109PubMedGoogle Scholar
  25. Leong ASY, Milos J, Tang SK (1993) Is immunolocalisation of proliferating cell nuclear antigen (PCNA) in paraffin sections a valid index of cell proliferation? Appl Immunohistochem 1:127–135Google Scholar
  26. Linden MD, Torres FX, Kubus J, Zarbo RJ (1992) Clinical application of morphologic and immunocytochemical assessments of cell proliferation. Am J Clin Pathol 97(Suppll): S4–S13PubMedGoogle Scholar
  27. Piacentini M, Autuori F, Dini L et al (1991) Tissue’ transglutaminase is specifically expressed in neonatal rat liver cells undergoing apoptosis upon epidermal growth factor stimulation. Cell Tissue Res 263: 227–235PubMedCrossRefGoogle Scholar
  28. Pritchard DJ, Butler WH (1989) Apoptosis- the mechanism of cell death in dimethylnitrosamine-induced hepatotoxicity. J Pathol 158: 253–260PubMedCrossRefGoogle Scholar
  29. Quinn CM, Wright NA (1990) The clinical assessment of proliferation and growth in human tumours: evaluation of methods and applications as prognostic variables. J Pathol 160:93–102PubMedCrossRefGoogle Scholar
  30. Ray SD, Sorge CL, Kamendulis LM, Corcoran GB (1992) Ca2+ activated DNA fragmentation and dimethylnitrosamine-induced hepatic necrosis: effects of Ca2+ endonuclease and poly (ADP-ribose) polymerase inhibitors in mice. J Pharmacol Exp Ther 263: 387–394PubMedGoogle Scholar
  31. Sarraf CE, McCormick CSF, Brown G, Price YE, Hall PA, Lane DP, Alison MR (1991) Proliferating cell nuclear antigen immunolocalization in gastro-intestinal epithelia. Digestion 50: 85–91PubMedCrossRefGoogle Scholar
  32. Schlüter C, Duchrow M, Wohlenberg C, Becker MHG, Key G, Flad H-D, Gerdes J (1993) The cell proliferation-associated antigen of antibody Ki-67: a very large, ubiquitous nuclear protein with numerous repeated elements, representing a new kind of cell cycle-maintaining proteins. J Cell Biol 123:513–522PubMedCrossRefGoogle Scholar
  33. Schwarting R (1993) Little missed markers and Ki-67. Lab Invest 68:597–599PubMedGoogle Scholar
  34. Steel GG (1977) Growth kinetics of tumours. Clarendon Press, OxfordGoogle Scholar
  35. Tomei LD, Shapiro JP, Cope FO (1993) Apoptosis in C3H/101/2 mouse embryonic cells: evidence for intemucleosomal DNA modification in the absence of double-strand DNA cleavage. Proc Natl Acad Sci 90: 853–857PubMedCrossRefGoogle Scholar
  36. Vaux DL (1993) Toward an understanding of the molecular mechanisms of physiological cell death. Proc Natl Acad Sci 90: 786–789PubMedCrossRefGoogle Scholar
  37. Waseem NH, Lane DP (1990) Monoclonal antibody analysis of the proliferating nuclear antigen (PCNA). J Cell Sci 96:121–129PubMedGoogle Scholar
  38. Wijsman JH, Jonker RR, Keijzer R, Van de Velde CJH, Cornlisse CJ, Van Dierendonck JH (1993) A new method to detect apoptosis in paraffin sections: in situ end-labelling of fragmented DNA. J Histochem Cytochem 41:7–12PubMedCrossRefGoogle Scholar
  39. Wright NA, Alison MR (1984) The biology of epithelial cell populations. Clarendon Press, Oxford Wyllie AH, Kerr JFR, Currie AR (1980) Cell death: the significance of apoptosis. Int. Rev Cytol 68: 251–306Google Scholar
  40. Zajicek G, Oren R, Weinreb JR (1985) The streaming liver. Liver 5: 293–300PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1994

Authors and Affiliations

  • Malcolm Alison
  • Matthew Golding
    • 1
  • Catherine Sarraf
    • 1
  1. 1.Deparment of HistopathologyRoyal Postgraduate Medical SchoolLondonUK

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