Cell Proliferation and Hepatocarcinogenesis

  • Michael Schwarz
  • Albrecht Buchmann
  • Larry W. Robertson
  • Werner Kunz


Chemically-induced hepatocarcinogenesis in rodents is a very useful tool to study qualitatively and quantitatively critical changes occurring during the carcinogenic process. There is strong evidence to suggest that enzyme-altered foci in liver are precursor lesions causally related to malignant transformation. In experiments with continuous exposure of rats to different doses of hepatocarcinogens the existence of quantitative relationships between the development of enzyme-altered foci and subsequent tumor manifestation in liver was demonstrated. The analysis of multiple enzyme markers indicated a marked heterogeneity of phenotypes between individual foci. Such diversity was also observed with respect to the growth properties of individual lesions and relationships between foci phenotype and proliferation rate were demonstrated. Our results suggest that not only the total number of enzyme-altered cells in liver but also the proliferation rate of individual cell clones is of major relevance for the transition(s) leading to malignant cell populations. In initiation-promotion experiments quantitative relationships between promoting activity of various xenobiotics and their potency to induce adaptive liver growth were established. Induction of cell proliferation in normal liver and in preneoplastic liver cells is therefore assumed to play an important role during the carcinogenic process.


Partial Hepatectomy Epoxide Hydrolase Volumetric Fraction Carcinogenic Process Liver Carcinogenesis 
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.

canalicular adenosine triphosphatase


cytochrome P-450


diethylnitrosamine (N-nitrosodiethylamine)








enzyme-altered foci


partial hepatectomy


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Copyright information

© Birkhäuser Boston 1990

Authors and Affiliations

  • Michael Schwarz
    • 1
  • Albrecht Buchmann
    • 1
  • Larry W. Robertson
    • 2
  • Werner Kunz
    • 1
  1. 1.Institute of BiochemistryGerman Cancer Research CenterHeidelbergGermany
  2. 2.Graduate Center for ToxicologyUniversity of KentuckyLexingtonUSA

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