Cell Proliferation and Cell Death in the Liver: Patterns, Mechanisms and Measurements
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).
KeywordsProliferate Cell Nuclear Antigen Littoral Cell Centrilobular Necrosis Apoptotic Hepatocyte Proliferative Cell Cycle
Unable to display preview. Download preview PDF.
- Alison MR, Sarraf CE (1992) Apoptosis: - a gene-directed programme of cell death. J R Coll Phys 26: 25–35Google Scholar
- 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
- 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
- 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
- Hall PA, Levison DA, Wright NA (eds) (1992) Assessment of cell proliferation in clinical practice. Springer-Verlag, London UKGoogle Scholar
- 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
- 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
- Steel GG (1977) Growth kinetics of tumours. Clarendon Press, OxfordGoogle Scholar
- 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