Thioacetamide accelerates steatohepatitis, cirrhosis and HCC by expressing HCV core protein in transgenic zebrafish Danio rerio

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-fo...

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Published inToxicology (Amsterdam) Vol. 243; no. 1; pp. 11 - 22
Main Authors Rekha, Ravikumar Deepa, Amali, Aseervatham Anusha, Her, Gour Mour, Yeh, Yang Hui, Gong, Hong-Yi, Hu, Shao-Yang, Lin, Gen-Hwa, Wu, Jen-Leih
Format Journal Article
LanguageEnglish
Published Shannon Elsevier Ireland Ltd 14.01.2008
Amsterdam Elsevier Science
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Abstract 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.
AbstractList 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.
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.
Author Her, Gour Mour
Hu, Shao-Yang
Yeh, Yang Hui
Wu, Jen-Leih
Amali, Aseervatham Anusha
Gong, Hong-Yi
Lin, Gen-Hwa
Rekha, Ravikumar Deepa
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Issue 1
Keywords thioacetamide
HCP
TAA
hepatitis C virus
HCC
Zebrafish
HCV
hepatocellular carcinoma
hepatitis C virus core protein
Thioacetamide
Hepatocellular carcinoma
Digestive system
Liver
Hepatic disease
Malignant tumor
Protein
Steatosis
Virus
Liver cancer
Cirrhosis
Vertebrata
Brachydanio rerio
Pisces
Digestive diseases
Flaviviridae
Hepatitis C virus
Hepacivirus
Cancer
Language English
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Snippet Abstract Hepatocellular carcinoma (HCC) is one of the common cancers worldwide, caused by Hepatitis C virus (HCV) and hepatotoxins. Here we report the...
Hepatocellular carcinoma (HCC) is one of the common cancers worldwide, caused by Hepatitis C virus (HCV) and hepatotoxins. Here we report the development of...
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SubjectTerms Animals
Animals, Genetically Modified
Biological and medical sciences
Carcinoma, Hepatocellular - chemically induced
Carcinoma, Hepatocellular - genetics
Carcinoma, Hepatocellular - virology
Chemical and Drug Induced Liver Injury
Danio rerio
DNA Primers
Emergency
Fatty Liver - chemically induced
Fatty Liver - genetics
Fatty Liver - virology
Gastroenterology. Liver. Pancreas. Abdomen
Hepacivirus - genetics
Hepatitis C virus
Hepatocellular carcinoma
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
Liver. Biliary tract. Portal circulation. Exocrine pancreas
Medical sciences
Microscopy, Confocal
Other diseases. Semiology
Reverse Transcriptase Polymerase Chain Reaction
Thioacetamide
Thioacetamide - toxicity
Toxicology
Tumors
Viral Core Proteins - genetics
Zebrafish
Zebrafish - genetics
Title Thioacetamide accelerates steatohepatitis, cirrhosis and HCC by expressing HCV core protein in transgenic zebrafish Danio rerio
URI https://www.clinicalkey.es/playcontent/1-s2.0-S0300483X07006348
https://dx.doi.org/10.1016/j.tox.2007.09.007
https://www.ncbi.nlm.nih.gov/pubmed/17997003
https://search.proquest.com/docview/19524049
Volume 243
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