ZFIN ID: ZDB-PUB-071118-45
Thioacetamide accelerates steatohepatitis, cirrhosis and HCC by expressing HCV core protein in transgenic zebrafish Danio rerio
Rekha, R.D., Amali, A.A., Her, G.M., Yeh, Y.H., Gong, H.Y., Hu, S.Y., Lin, G.H., and Wu, J.L.
Date: 2008
Source: Toxicology   243(1-2): 11-22 (Journal)
Registered Authors: Gong, Hong-Yi, Her, Guor Muor, Lin, Gen-Hwa, Wu, Jen-Leih
Keywords: Hepatocellular carcinoma, Thioacetamide, Zebrafish
MeSH Terms:
  • Animals
  • Animals, Genetically Modified
  • Carcinoma, Hepatocellular/chemically induced
  • Carcinoma, Hepatocellular/genetics
  • Carcinoma, Hepatocellular/virology
  • Chemical and Drug Induced Liver Injury
  • DNA Primers
  • Fatty Liver/chemically induced
  • Fatty Liver/genetics
  • Fatty Liver/virology
  • Hepacivirus/genetics*
  • Liver/drug effects
  • Liver/metabolism
  • Liver/pathology
  • Liver Cirrhosis/chemically induced
  • Liver Cirrhosis/genetics
  • Liver Cirrhosis/virology
  • Liver Diseases*/genetics
  • Liver Diseases*/virology
  • Liver Neoplasms/chemically induced
  • Liver Neoplasms/genetics
  • Liver Neoplasms/virology
  • Microscopy, Confocal
  • Reverse Transcriptase Polymerase Chain Reaction
  • Thioacetamide/toxicity*
  • Viral Core Proteins/genetics*
  • Zebrafish/genetics*
PubMed: 17997003 Full text @ Toxicology
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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.
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