Role of cell proliferation at early stages of hepatocarcinogenesis

Toxicology Letters
M SchwarzK W Bock

Abstract

Hepatocarcinogenesis in rodents is characterized by the early appearance of foci of enzyme-altered (initiated) cells which are believed to represent precursors on the way to malignancy. Proliferation of cells within enzyme-altered liver foci is generally increased as compared to surrounding normal hepatocytes. This may be mediated by changes in the rates of cell division and/or cell death (apoptosis). Cell proliferation is controlled by complex signaling networks and may be modulated by xenobiotics. In mouse--but not rat or human--liver, mutation of the Ha-ras gene appears to represent a critical genetic alteration which may confer a selective growth advantage to the mutated cells. Exogenous tumor-promoting agents may stimulate cell division and depress apoptosis of preneoplastic hepatocytes, thereby increasing the probability of cancer. By means of histochemical methods, data on the frequencies of both cell division and cell death can be collected separately and utilized for estimation of promoter efficacy. In addition, quantitative stereology may be applied to the analysis of the size distribution of enzyme-altered foci and used for modeling of hepatocarcinogenesis.

References

Jun 1, 1992·Trends in Pharmacological Sciences·W BurschR Schulte-Hermann
Feb 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·A BuchmannM Schwarz
Jan 1, 1990·Annual Review of Pharmacology and Toxicology·H C Pitot
Aug 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·R W WisemanJ A Miller
Jan 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·S H ReynoldsS A Aaronson
Jan 1, 1986·Annual Review of Public Health·S H Moolgavkar
Aug 1, 1985·Archives of Toxicology·R Schulte-Hermann
Dec 1, 1995·Mutation Research·M SchwarzK W Bock

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Citations

Mar 15, 2006·Neoplasia : an International Journal for Oncology Research·Patrick J KleinJudith S Sebolt-Leopold
Jun 21, 2005·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Sabine StahlMichael Schwarz
Jan 16, 2007·Molecular Carcinogenesis·Volodymyr P TryndyakIgor P Pogribny

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