We have analyzed the histological changes in rat liver after 2-acetylaminof
luorene (AAF) administration. The data demonstrate that AAF-induced oval ce
lls were preferentially generated by proliferation of the terminal biliary
ductules that we suggest constitute the primary hepatic stem cell niche. Th
e oval cells formed ductular structures, representing an extension of the c
anals of Hering. This histological organization provides continuous bile dr
ainage of the hepatocytes and uninterrupted blood flow in the sinusoids. Th
e oval cell ductules are surrounded by a continuous basement membrane that
is intermittently disrupted by processes of stellate cells that form direct
cell-cell contact with the oval cells. Although both AAF treatment and bil
e duct Ligation results In proliferation of biliary epithelial cells, the m
echanism(s) responsible for the proliferation of the biliary epithelium see
ms to differ in the two models. in contrast to the biliary proliferation st
imulated by bile ligation, AAF-induced oval cell proliferation as well as t
he capacity of these cells to differentiate into hepatocytes, bile epitheli
al cells and possibly other cell lineages can be blocked by administration
of dexamethasone.