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Characteristics of Dehydroepiandrosterone-induced Hepatocarcinogenesis in the Rat

  • Doris Mayer
  • Christel Metzger
  • Dirk Nehrbass
  • Peter Bannasch
Conference paper

Summary

Dehydroepiandrosterone (DHEA) induces and enhances hepatocarcinogenesis in the rat, the tumor incidence being higher in females than in males. Preneoplastic and neoplastic lesions induced by DHEA belong to the amphophilic cell lineage of hepatocarcinogenesis. Moreover, DHEA modulates preneoplastic liver foci of the glycogenotic/basophilic cell lineage induced by the hepatocarcinogen N-nitrosomorpholine (NNM) to amphophilic cell foci (APF). This process is associated with profound changes in the expression of key enzymes of energy metabolism and a down-regulation of the expression of insulin receptor substrate-1, a signaling molecule activated by tyrosine kinase receptors, which is over-expressed in glycogenotic lesions. This suggests a cross-talk of the steroid-mediated signaling pathway with tyrosine kinase receptor-activated signal transduction pathways during enhancement of hepatocarcinogenesis by DHEA.

Keywords

Glycogen Content Peroxisome Proliferation Tumor Incidence Preneoplastic Lesion Cell Focus 
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. 1.
    Rao MS, Subbarao V, Yeldandi AV et al. (1992) Hepatocarcinogenicity of dehydroepiandrosterone in the rat. Cancer Res 52:2977–2979.PubMedGoogle Scholar
  2. 2.
    Metzger C, Mayer D, Hoffmann H et al. (1995) Sequential appearance and ultrastructure of amphophilic cell foci, adenomas, and carcinomas in the liver of male and female rats treated with dehydroepiandrosterone. Toxicol Pathol 23:591–605.PubMedCrossRefGoogle Scholar
  3. 3.
    Orner GA, Mathews C, Hendricks JD et al. (1995) Dehydroepiandrosterone is a complete hepatocarcinogen and potent tumor promoter in the absence of peroxisome proliferation in rainbow trout. Carcinogenesis 16:2893–2898.PubMedCrossRefGoogle Scholar
  4. 4.
    Bannasch P (1996) Pathogenesis of hepatocellular carcinoma: Sequential cellular, molecular, and metabolic changes. Prog Liver Dis 14:161–197.PubMedGoogle Scholar
  5. 5.
    Bannasch P, Klimek F, Mayer D (1997) Early bioenergetic changes in hepatocarcinogenesis: preneoplastic phenotypes mimic responses to insulin and thyroid hormone. J Bioenerg Biomembr 29:303–313.PubMedCrossRefGoogle Scholar
  6. 6.
    Mayer D, Metzger C, Leonetti P et al. (1998) Differential expression of key enzymes of energy metabolism in preneoplastic and neoplastic rat liver lesions induced by N-nitrosomorpholine and dehydroepiandrosterone. Int J Cancer (Pred Oncol) 79:232–240.CrossRefGoogle Scholar
  7. 7.
    Metzger C, Bannasch P, Mayer D (1997) Enhancement and phenotypic modulation of N-nitrosomorpholine-induced hepatocarcinogenesis by dehydroepiandrosterone. Cancer Lett 121:125–131.PubMedCrossRefGoogle Scholar
  8. 8.
    NehrbaB D, Klimek F, Mayer D et al. (1998) Differential expression of insulin receptor substrate-1 in various types of preneoplastic hepatic foci. Proc Amer Assoc Cancer Res 39:485.Google Scholar
  9. 9.
    NehrbaB D, Klimek F, Bannasch P (1998) Overexpression of insulin receptor substrate-1 emerges early in hepatocarcinogenesis and elicits preneoplastic hepatic glycogenosis. Am J Pathol 152:341–345.Google Scholar
  10. 10.
    Gabriel KR, Odoroff CL (1990) Biplots in biomedical research. Statistics in Medicine 9:469–485.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag New York, Inc. 2001

Authors and Affiliations

  • Doris Mayer
  • Christel Metzger
  • Dirk Nehrbass
  • Peter Bannasch

There are no affiliations available

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