Stem cell activation in the acetylaminofluorene-treated regenerating rat liver: a bile ductular reaction?

Document Type

Book Chapter


Pathology and Laboratory Medicine


The ability of the liver to regenerate in response to the loss of hepatocytes is widely recognised, and this is usually accomplished by the triggering of normally proliferativekly quiescent hepatocytes into the cell cycle (Wright and Alison 1984; Alison 1986). Liver regeneration is commonly studied in the rat after a two-thirds partial hepatectomy. However, when hepatocyte regeneration is impaired, then relatively undifferentiated cells emerge from the portal space and take over the burden of regenerative growth. These potential stem cells are called oval cells (Sell 1990) and they are seen in chronically damaged human liver (De Vos and Desmet 1992), in galactosamine poisoned rats (Lemire et al 1991; Dabeva and Shafritz 1993) and when hepatocyte regeneration is prevented by the presence of cytotoxic carcinogens (Alison and Hully 1991). The antiproliferative effects of chemical carcinogens were recognised by Haddow in 1935 and this property has been exploited in the development of the so-called ‘Resistant Hepatocyte’ model of carcinogenesis (Soit et al 1977) whereby rats injected with the genotoxic chemical diethylnitrosamine developed basophilic liver cell foci shortly after being partially hepatectomised while being fed 2-acetylaminofluorene (2-AAF). 2-AAF prevents hepatocyte regeneration, but initiated oval cells can escape (resist) this inhibition and divide and eventually form dysplastic foci (Alison and Hully 1991).


Liver Carcinogenesis