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

• Published in: Toxicology (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
• Language: English
• Published: Shannon Elsevier Ireland Ltd 14.01.2008; Amsterdam Elsevier Science
• Subjects: 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; 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
• ISSN: 0300-483X; 1879-3185
• DOI: 10.1016/j.tox.2007.09.007

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.