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Hepatic iron overload induces hepatocellular carcinoma in transgenic mice expressing the hepatitis C virus polyprotein.
Gastroenterology. 2006 Jun; 130(7):2087-98.G

Abstract

BACKGROUND & AIMS

Despite the evidence of hepatic iron overload in patients with chronic hepatitis C, it remains unknown if iron overload is related to hepatocarcinogenesis in this condition. The aim of this study was to determine whether iron overload contributes to development of hepatocellular carcinoma (HCC) in transgenic mice expressing the hepatitis C virus (HCV) polyprotein.

METHODS

Male C57BL/6 transgenic mice expressing the HCV polyprotein and nontransgenic littermates were fed an excess-iron diet or control diet. Mice in each group were assessed for altered liver morphology and function and the development of liver tumors.

RESULTS

Hepatic iron concentrations in mice fed the excess-iron diet were comparable to those of patients with chronic hepatitis C. There was no inflammation in transgenic and nontransgenic livers. Compared with mice in 3 other groups, transgenic mice fed the excess-iron diet showed marked hepatic steatosis including the centrilobular microvesicular type, ultrastructural alterations of the mitochondria and decreased degradation activity of fatty acid at 6 months, and greater hepatic content of lipid peroxidation products and 8-hydroxy-2'-deoxyguanosine at 12 months after initiation of feeding. The number of proliferating hepatocytes was significantly increased in mice fed the excess-iron diet but was not different between transgenic and nontransgenic mice. Hepatic tumors including HCC developed in 5 of 11 (45%) transgenic mice fed the excess-iron diet but not in mice in other groups at 12 months after initiation of feeding.

CONCLUSIONS

Iron overload induces mitochondrial injury and increases the risk of HCC development in transgenic mice expressing the HCV polyprotein.

Authors+Show Affiliations

Department of Gastroenterology and Hepatology, Yamaguchi University School of Medicine, Ube, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16762631

Citation

Furutani, Takakazu, et al. "Hepatic Iron Overload Induces Hepatocellular Carcinoma in Transgenic Mice Expressing the Hepatitis C Virus Polyprotein." Gastroenterology, vol. 130, no. 7, 2006, pp. 2087-98.
Furutani T, Hino K, Okuda M, et al. Hepatic iron overload induces hepatocellular carcinoma in transgenic mice expressing the hepatitis C virus polyprotein. Gastroenterology. 2006;130(7):2087-98.
Furutani, T., Hino, K., Okuda, M., Gondo, T., Nishina, S., Kitase, A., Korenaga, M., Xiao, S. Y., Weinman, S. A., Lemon, S. M., Sakaida, I., & Okita, K. (2006). Hepatic iron overload induces hepatocellular carcinoma in transgenic mice expressing the hepatitis C virus polyprotein. Gastroenterology, 130(7), 2087-98.
Furutani T, et al. Hepatic Iron Overload Induces Hepatocellular Carcinoma in Transgenic Mice Expressing the Hepatitis C Virus Polyprotein. Gastroenterology. 2006;130(7):2087-98. PubMed PMID: 16762631.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hepatic iron overload induces hepatocellular carcinoma in transgenic mice expressing the hepatitis C virus polyprotein. AU - Furutani,Takakazu, AU - Hino,Keisuke, AU - Okuda,Michiari, AU - Gondo,Toshikazu, AU - Nishina,Sohji, AU - Kitase,Akira, AU - Korenaga,Masaaki, AU - Xiao,Shu-Yuan, AU - Weinman,Steven A, AU - Lemon,Stanley M, AU - Sakaida,Isao, AU - Okita,Kiwamu, PY - 2005/11/07/received PY - 2006/02/22/accepted PY - 2006/6/10/pubmed PY - 2006/7/19/medline PY - 2006/6/10/entrez SP - 2087 EP - 98 JF - Gastroenterology JO - Gastroenterology VL - 130 IS - 7 N2 - BACKGROUND & AIMS: Despite the evidence of hepatic iron overload in patients with chronic hepatitis C, it remains unknown if iron overload is related to hepatocarcinogenesis in this condition. The aim of this study was to determine whether iron overload contributes to development of hepatocellular carcinoma (HCC) in transgenic mice expressing the hepatitis C virus (HCV) polyprotein. METHODS: Male C57BL/6 transgenic mice expressing the HCV polyprotein and nontransgenic littermates were fed an excess-iron diet or control diet. Mice in each group were assessed for altered liver morphology and function and the development of liver tumors. RESULTS: Hepatic iron concentrations in mice fed the excess-iron diet were comparable to those of patients with chronic hepatitis C. There was no inflammation in transgenic and nontransgenic livers. Compared with mice in 3 other groups, transgenic mice fed the excess-iron diet showed marked hepatic steatosis including the centrilobular microvesicular type, ultrastructural alterations of the mitochondria and decreased degradation activity of fatty acid at 6 months, and greater hepatic content of lipid peroxidation products and 8-hydroxy-2'-deoxyguanosine at 12 months after initiation of feeding. The number of proliferating hepatocytes was significantly increased in mice fed the excess-iron diet but was not different between transgenic and nontransgenic mice. Hepatic tumors including HCC developed in 5 of 11 (45%) transgenic mice fed the excess-iron diet but not in mice in other groups at 12 months after initiation of feeding. CONCLUSIONS: Iron overload induces mitochondrial injury and increases the risk of HCC development in transgenic mice expressing the HCV polyprotein. SN - 0016-5085 UR - https://www.unboundmedicine.com/medline/citation/16762631/Hepatic_iron_overload_induces_hepatocellular_carcinoma_in_transgenic_mice_expressing_the_hepatitis_C_virus_polyprotein_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0016-5085(06)00741-4 DB - PRIME DP - Unbound Medicine ER -