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Bile acid secretion during rat liver carcinogenesis
M J Monte1, F Palomero, G R Sainz
1Departamento de Fisiología y Farmacología, Universidad de Salamanca, Spain.
Life Sciences
|March 29, 2000
Summary
Liver tumor development alters bile acid secretion. Bile acid output initially drops, then recovers, and falls again during carcinoma. Bile acid composition also changes significantly during rat hepatocarcinogenesis.
Area of Science:
- Hepatology
- Cancer Biology
- Biochemistry
Background:
- Neoplastic liver processes involve retro-differentiation and tumor antigen expression.
- Understanding how liver function, like bile acid secretion, is affected is crucial.
Purpose of the Study:
- To investigate alterations in bile acid secretion during rat hepatocarcinogenesis.
- To correlate changes in bile acid secretion with different stages of liver tumor development.
Main Methods:
- Rat hepatocarcinogenesis induced by diethylnitrosamine, partial hepatectomy, and 2-acetamidofluorene.
- Development of a novel monoclonal antibody (MAb 14.1.3) against placental glutathione-S-transferase (GST-P).
- Analysis of bile acid output, bile flow, and bile acid composition (cholic acid, chenodeoxycholic acid, glycine/taurine conjugation) at various time points.
Main Results:
- Significant reduction in total biliary bile acid output during GST-P-positive foci formation (-26%) at 12 wk.
- Bile acid output normalized during adenoma formation but decreased again during carcinoma transformation.
- Progressive increase in cholic acid-to-chenodeoxycholic acid ratio and a transient increase in glycine-amidated bile acids observed during tumor progression.
Conclusions:
- Bile acid secretion mechanisms are differentially modified at various stages of rat liver tumor development.
- Changes in bile acid secretion are not directly parallel to bile flow alterations.
- Specific modifications in bile acid composition suggest distinct functional changes during hepatocarcinogenesis.