Hypomethylation of c-myc Proto-oncogene of N-Nitrosomorpholine — Induced Rat Liver Nodules and of H4IIE Cells

  • P. Münzel
  • K. W. Bock
Part of the Archives of Toxicology book series (TOXICOLOGY, volume 13)


In rat hepatocarcinogenesis, inheritable alterations of clonally expanding hepatocytes which lead to permanent changes of carbohydrate and drug metabolism can be visualized histochemically. For example, a 3-methylcholanthrene-inducible UDP-glucuronyltransferase isozyme is permanently increased in rat liver foci (Fischer et al 1985) and nodules (Bock et al 1982). Multiple mechanisms are presumably responsible for the above alterations. NAD(P)H quinone reductase is permanently increased in liver nodules, and in this case the gene has been shown to be hypomethylated (Williams et al 1986). Methylation is often associated with decreased gene expression. DNA binding of 2-acetylaminofluorene inhibited the ability of cytosine 5-methyltransferase to methylate native DNA (Pfohl-Leszkowicz et al 1981). This finding suggests that epigenetic alterations such as hypomethylation may be indirect consequences of genotoxic lesions. The present study aimed at investigating the methylation status of c-myc as a possible critical target gene responsible for hepatocyte growth control.


Quinone Reductase Liver Nodule Decrease Gene Expression H4IIE Cell General Mechanism Responsi 
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Copyright information

© Springer-Verlag Berlin Heidelberg 1989

Authors and Affiliations

  • P. Münzel
    • 1
  • K. W. Bock
    • 1
  1. 1.Institute of Toxicology, University of TübingenTübingenFed. Rep. Germany

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