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Updated: Aug 19, 2026
An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis
Published on: September 12, 2019
Oncosis represents the main type of cell death in mouse models of cholestasis
Peter Fickert1, Michael Trauner, Andrea Fuchsbichler
1Laboratory of Experimental Hepatology, Division of Gastroenterology and Hepatology, Department of Medicine, Medical University, Auenbruggerplatz 15, A-8036 Graz, Austria. peter.fickert@klinikum-graz.at
Background/Aims:
Since the mechanisms leading to hepatocyte death in cholestasis are not well defined, we aimed to obtain closer insights into the related pathogenetic principles.
Methods:
Cell death was assessed in common bile duct ligated (CBDL) and cholic acid (CA)-fed mice, and compared to Fas agonist Jo2-injected mice by studying H and E-stained tissue sections, DNA ladder analysis, caspase-3-like activity assay, immunohistochemistry, double immunofluorescence microscopy for activated caspase-3 and cytokeratin (CK) 18, the TUNEL method, and electron microscopy.
Results:
Jo2-treated mice showed activation of caspase-3, breakdown of the CK intermediate filament network, and classical morphological features of apoptosis. In contrast, in CA-fed and CBDL mice, oncosis characterized by cell swelling and ruptured cell membranes was the predominant type of cell death, whereas in both experimental conditions significant activation of caspase-3 was absent and typical CK alterations were rare despite frequent positivity of the TUNEL assay.
Conclusions:
(i) Oncosis represents the main type of hepatocyte death in acute cholestasis in mice. (ii) The importance of apoptosis in cholestasis may be overestimated if non-specific detection systems (e.g. TUNEL assay) are used.
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