Thioacetamide accelerates steatohepatitis, cirrhosis and HCC by expressing HCV core protein in transgenic zebrafish Danio rerio
Resource
Toxicology 243 (1-2): 11-22
Journal
Toxicology
Pages
11
Date Issued
2008
Date
2008
Author(s)
Rekha, Ravikumar Deepa
Amali, Aseervatham Anusha
Her, Gour Mour
Yeh, Yang Hui
Gong, Hong-Yi
Hu, Shao-Yang
Lin, Gen-Hwa
Wu, Jen-Leih
Abstract
Hepatocellular carcinoma (HCC) is one of the common cancers worldwide, caused by Hepatitis C virus (HCV) and hepatotoxins. Here we report the development of HCC in wild type as well as HCV core protein (HCP)-transgenic zebrafish upon treatment with a hepatotoxin, thioacetamide (TAA). Two-fold accelerated HCC development could be achieved in the TAA-treated transgenic fish, that is, the progression of the disease in TAA-treated wild type zebrafish developed HCC in 12 weeks whereas that of HCP-transgenic zebrafish shortened the HCC progression to 6 weeks. Histopathological observation showed the specific pathological features of HCC. The HCC progression was confirmed through RT-PCR that revealed an up and down regulation of different marker genes at various stages of HCC progression such as, steatohepatitis, fibrosis and HCC. Moreover, HCV core protein expressed in the HCP-transgenic zebrafish and TAA synergistically accelerate the HCC development. It must be mentioned that, this is the first report revealing HCV core protein along with TAA to induce HCC in zebrafish, particularly, in a short period of time comparing to mice model. As zebrafish has already been considered as a good human disease model and in this context, this HCC-zebrafish model may serve as a powerful preclinical platform to study the molecular events in hepatocarcinogenesis, therapeutic strategies and for evaluating chemoprevention strategies in HCC. ? 2007 Elsevier Ireland Ltd. All rights reserved.
Subjects
Hepatocellular carcinoma; Thioacetamide; Zebrafish
SDGs
Other Subjects
core protein; thioacetamide; animal experiment; animal model; animal tissue; article; cancer model; controlled study; down regulation; fatty liver; gene expression regulation; Hepatitis C virus; histopathology; liver carcinogenesis; liver cell carcinoma; liver cirrhosis; nonhuman; priority journal; protein function; reverse transcription polymerase chain reaction; steatohepatitis; transgenic animal; upregulation; zebra fish; Animals; Animals, Genetically Modified; Carcinoma, Hepatocellular; DNA Primers; Fatty Liver; Hepacivirus; Liver; Liver Cirrhosis; Liver Diseases; Liver Neoplasms; Microscopy, Confocal; Reverse Transcriptase Polymerase Chain Reaction; Thioacetamide; Viral Core Proteins; Zebrafish; Danio rerio; Hepatitis C virus; Mus
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