DSpace Collection:
https://hdl.handle.net/10171/51798
2024-03-29T00:13:23ZLiver Damage using Suicide Genes A Model for Oval Cell Activation
https://hdl.handle.net/10171/23390
Title: Liver Damage using Suicide Genes A Model for Oval Cell Activation
Abstract: Liver regeneration from the facultative hepatic stem cells, the oval cells, takes
place in situations in which liver regeneration from pre-existing hepatocytes is
prevented. Different models have been used to stimulate oval cell response. Many
of them involve the use of carcinogenic agents with or without partial
hepatectomy. In this study we show that adenovirus-mediated gene transfer of the
suicide gene thymidine kinase followed by ganciclovir administration caused
hepatotoxicity of variable intensity. Rats with moderate elevation in serum
transaminases recovered normal liver architecture few weeks after adenovirus
injection. In contrast, rats with severe liver damage exhibited a marked and
persisting activation of oval cells accompanied by ductular hyperplasia. In some
rats, such lesion eventually evolved to cholangiofibrosis and in one rat to
cholangiocarcinoma. Deposition of fibronectin and increased number of hepatic
stellate cells were found in association with oval cells and cholangiofibrotic
lesions. Hepatocyte growth factor was hyperexpressed in the livers with intense
oval cell response or ductular proliferation, suggesting a participation of this
factor in those lesions. In summary, our data demonstrate activation of oval cell
response after gene transfer of thymidine kinase followed by ganciclovir
administration. These findings indicate that high doses of this therapy causes
liver damage together with an impairment in hepatocellular regeneration.2000-01-01T00:00:00Z