Differentiation of oval cells into duct-like cells in preneoplastic liver of rats placed on a choline-deficient diet supplemented with ethionine.
Feeding male Wistar rats a choline-deficient diet containing 0.07% DL-ethionine (CDE diet) for up to 5 weeks results in the production of two distinct non-parenchymal cell populations, oval and duct-like cells. These cells can undergo replication and display different patterns of expression of glutathione S-transferases (GSTs) and pyruvate kinases (PKs). Oval cells were first detected around the periportal region after 1 week of CDE treatment and infiltrated the parenchyma after 2 weeks. Duct-like structures first appeared as isolated ducts in the parenchymal region at 2 weeks and were easily detected after 2.5 weeks. These duct-like structures differed from the bile ducts which reside in the portal region. Large concentrations of duct-like structures in cyst-like clusters were detected after 5 weeks. Enlargement of these structures from single ducts to clusters of up to 20 ducts was observed over 3-5 weeks of CDE treatment. The number of cells forming a duct increased from 5 to 30 cells. We established a double immunocytochemical staining technique to characterize the oval and duct-like cells for their expression of GSTs and PKs. pi GST and M2-PK, which are fetal hepatocytes isoenzymes, are present in virtually all the oval and duct-like cells. Most of the oval cells are devoid of the adult hepatocytes markers, alpha GST, mu GST and L-PK. There are two sub-populations of duct-like cells, one which expresses only fetal markers and the other which co-expresses the adult and fetal isoenzymes. Hence, oval cells display characteristics of fetal hepatocytes and some duct-like cells appear more mature than oval cells. Using a combination of double immunocytochemical and [3H]thymidine labelling techniques we have established that oval cells differentiate into duct-like cells.
Tee
L B
LB
Department of Physiology, University of Western Australia, Nedlands.
Kirilak
Y
Y
Huang
W H
WH
Morgan
R H
RH
Yeoh
G C
GC
D000818:Animals; D001652:Bile Ducts / Q000737:chemistry; D015415:Biomarkers; D002454:Cell Differentiation / Q000187:drug effects; D002796:Choline Deficiency / Q000473:pathology*; D004798:Enzymes / Q000032:analysis; D005001:Ethionine / Q000494:pharmacology* / Q000633:toxicity; D005326:Fetal Proteins / Q000032:analysis; D007124:Immunoenzyme Techniques; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008107:Liver Diseases / Q000209:etiology / Q000473:pathology*; D008297:Male; D011230:Precancerous Conditions / Q000209:etiology / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D013234:Stem Cells / Q000187:drug effects / Q000473:pathology
D015415:Biomarkers; D004798:Enzymes; D005326:Fetal Proteins; D005001:Ethionine