title: Hepatic oval cell lines generate hepatocellular carcinoma following transfection with HBx gene and treatment with aflatoxin B1 in vivo.
abstract: Hepatic oval cells (HOC) are considered to be the stem cells of the liver and have been linked to the development of hepatic malignancies. Studies have demonstrated that chronic hepatitis B virus (HBV) infection and dietary aflatoxin B1 (AFB1) exposure are among the most important risk factors for the development of hepatocellular carcinoma (HCC). However, little research has been done to evaluate the role of oval cells in these two environmental factors on hepatocarcinogenesis. In this study, partial transformation of rat HOC (LE/6) were accomplished by transfected HBV x gene (HBx), and then transfected cells were implanted both intra-hepatically and subcutaneously into nude mice treated with AFB1 in vivo. We found the oval cells produced tumors (4/24 of the animals) in liver following transfection with HBx gene and treatment with AFB1. These intrahepatic tumors included HCC cells (immunopositive for HepParl, ALB, CK8 and AFP) and mesenchymal cells (immunopositive for Vimentin and SMA). Whereas mesenchymal tumors were observed at the subcutaneous tissue with a similar rate in all controls treated with cell lines (10/24 in HBx-oval cells/AFB1 group, 8/20 in HBx-oval cells/non-AFB1 group, 10/20 in non-HBx/AFB1 group; 9/20 in non-HBx/non-AFB1 group). Conversely, none of the controls developed intrahepatic tumors. These results provide an evidence that oval cells have the capacity to generate HCC through the combined effects of the HBx and AFB1 in the liver microenvironment.
authors.affiliation: Hepatic Surgery Centre, Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China.
authors.forename: Chang-Hai
authors.initials: CH
authors.lastname: Li
authors.forename: Yan-Jun
authors.initials: YJ
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Dong
authors.forename: Shuai
authors.initials: S
authors.lastname: Xiang
authors.forename: Hui-Fang
authors.initials: HF
authors.lastname: Liang
authors.forename: Heng-Yi
authors.initials: HY
authors.lastname: Wang
authors.forename: Han-Hua
authors.initials: HH
authors.lastname: Dong
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Chen
mesh_terms: D016604:Aflatoxin B1 / Q000494:pharmacology*; D000818:Animals; D045744:Cell Line, Tumor; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D051381:Rats; D015534:Trans-Activators / Q000235:genetics*; D014162:Transfection; D054334:Viral Regulatory and Accessory Proteins
chemical_list: D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; D016604:Aflatoxin B1