Skip to content

Advertisement

  • Meeting abstract
  • Open Access

Role of mesenchymal liver cells in mediating hepatic toxicity and carcinogenesis

  • 1,
  • 1,
  • 1,
  • 1,
  • 1 and
  • 1Email author
BMC Pharmacology20077 (Suppl 2) :A58

https://doi.org/10.1186/1471-2210-7-S2-A58

  • Published:

Keywords

  • Growth Factor
  • Arsenic
  • Phenobarbital
  • Mesenchymal Cell
  • Kupffer Cell

Mesenchymal liver cells (Kupffer cells, KC; sinusendothelial cells, EC) are considered to play a role in the response of the liver to pro-inflammatory stimuli. We studied whether genotoxic and non-genotxic carcinogens are also capable to activate these mesenchymal liver cells. Liver cell suspensions were separated into hepatocytes, KC and EC. Cells were incubated with lipopolysaccharid (LPS), the genotoxic N-nitrosomorpholine (NNM) or non-genotoxic carcinogens like nafenopin, cyproterone acetate, phenobarbital, or arsenic. LPS and NNM incuced a release of TNF-α and superoxide while the other compounds showed mostly minor effects on KC and EC. To assess the impact of activated mesenchymal cells on hepatocarcinogenesis a co-culture model of unaltered and preneoplastic hepatocytes was used. DNA synthesis was significantly higher in preneoplastic than unaltered cells and was further increased by supernatant of LPS-stimulated KC and EC. The supernatant effect was greatly abrogated by antisera neutralizing heparin-binding epidermal growth factor-like growth factor (HB-EGF). HB-EGF itself was a potent inducer of DNA synthesis and mitosis preferentially in the preneoplastic hepatocytes. In conclusion, KC and EC, activated by pro-inflammatory stimuli, may contribute to carcinogenesis via release of growth factors for preneoplastic hepatocytes. Whether this cell activation may be caused by non-genotoxic carcinogens requires further investigations.

Authors’ Affiliations

(1)
Department of Medicine I, Institute of Cancer Research, Medical University of Vienna, Austria

Copyright

© Sagmeister et al; licensee BioMed Central Ltd. 2007

This article is published under license to BioMed Central Ltd.

Advertisement