Expression of L- and M2-pyruvate kinases in proliferating oval cells and cholangiocellular lesions developing in the livers of rats fed a methyl-deficient diet.

Male outbred Sprague-Dawley rats were fed a choline-deficient diet containing 0.1% w/w DL-ethionine (CDE) for up to 22 weeks. The expression of the pyruvate kinase isoenzymes L (L-PK) and M2 (M2-PK) was immunohistochemically analyzed in liver slices from rats killed 4, 10, 14 and 22 weeks after starting the treatment. M2-PK was detected in bile duct epithelial cells of untreated rats and in proliferating oval cells, cholangiofibroses and cholangiofibromas of CDE-fed animals. Thus, M2-PK can be viewed as a positive marker of the bile duct epithelial/oval cell compartment. L-PK, a parenchymal cell-specific protein in untreated rat liver, was not present in proliferating oval cells, but was consistently observed in cells that were part of the ductal structures in the cholangiofibroses and cholangiofibromas. Based on their morphology, the L-PK-positive duct cells were undoubtedly part of the bile duct epithelial cell lineage and no L-PK-positive hepatocyte-like cells were observed in the ducts. Hence, this study clearly shows that the mere presence of a liver parenchymal cell marker in cells of the bile duct epithelial/oval cell compartment does not necessarily preclude that these cells are undergoing a differentiation into preneoplastic parenchymal cells, as has previously been suggested.