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© 1995 Oxford University Press
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Transplantation of normal hepatocytes modulates the development of chronic liver lesions induced by a pyrrolizidine alkaloid, lasiocarpinet
1Istituto di Patologia Spermantale, Unviersità di Caglian Cagliari
2Ospedale Oncologico ‘A.Busineco’ USL 21,Cagliari, Italy
3Department of Pathology, University of Toronto Toronto, Canada
4To whom reprint requests should be addressed at: Istituto di Patologia Sperimentale, Università di Cagliari Via Porcell 4, 09124, Cagliari, Italy
Laipcarpine (LC), a pyorrolizidine alkaloid, is able to induce a series of chronic and progressive lesions in rat liver, includinga long-lasting block in the cell cycle, the appearance of enlarged hepatocytes (megalocytosis), fibrosis, cirrhosis and malignant neoplasms. In this study the effect of transplantation of normal hepatocytes on the development of LC (80 µmol/kg i.p.). Four weeks later all animals were subjected to 2/3 paroticl hepatectomy (PH). In addition, at the time of PH one group of rats were transplanted with normal hepatocytes isolated from a syngeneic donor (106 cells/rat via the portal vein), while the other group received only the culture medium. All rats were killed 14 weeks after the operation. Grossly, the liver of rats exposed to LC followed by PH with no transplantation of normal hepatocytes was small in size (% liver wt/body wt 1.66 ± 0.08) and exhibited a few whitish nodules. Histologically, 
88% of the liversection was occupied by enlarged hepatocytes and hepatocyte nodules composed of smaller hepatocytes developed in every animal in this groupo. In addition, extensive bile ductular proliferation was present. However, the liver of rats that were significantly larger in size (% liver wt/body wt 2.16 ± 0.07) and were almost completely free of megalocytosis, bile ductular proliferation was hepatocyte nodule. These findings indicate that transplantation of normal hepatocytes is able to modulate the development of kchronic liver lesions induced by LC and may be relevant to the pathogenesis of progressive liver diseases suchas neoplasia and cirrhosis.
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