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Mouse models are essential tools for investigating the pathogenesis of HCC; however, the overwhelming majority of cancer models in rodents do not feature liver fibrosis. Detailed in this unit is a protocol for an experimental mouse model of HCC that arises in association with advanced liver fibrosis. The disease model is induced by a single injection of <jats:italic>N<\/jats:italic>\u2010nitrosodiethylamine (DEN) followed by repeated administration of carbon tetrachloride (CCl<jats:sub>4<\/jats:sub>). A dramatic potentiation of liver tumor incidence is observed following administration of DEN and CCl<jats:sub>4<\/jats:sub>, with100% of mice developing liver tumors at 5 months of age. This model can be employed for studying the molecular mechanisms of fibrogenesis and HCC development, and in cancer hazard\/chemotherapy testing of drug candidates. <jats:italic>Curr. Protoc. Pharmacol<\/jats:italic>. 66:14.30.1\u201014.30.10. \u00a9 2014 by John Wiley &amp; Sons, Inc.<\/jats:p>","DOI":"10.1002\/0471141755.ph1430s66","type":"journal-article","created":{"date-parts":[[2014,9,2]],"date-time":"2014-09-02T13:20:39Z","timestamp":1409664039000},"source":"Crossref","is-referenced-by-count":123,"title":["The DEN and CCl<sub>4<\/sub>\u2010Induced Mouse Model of Fibrosis and Inflammation\u2010Associated Hepatocellular Carcinoma"],"prefix":"10.1002","volume":"66","author":[{"given":"Takeki","family":"Uehara","sequence":"first","affiliation":[{"name":"Department of Environmental Sciences and Engineering, University of North Carolina  Chapel Hill North Carolina"},{"name":"Strategic Development Department, Shionogi &amp; Co  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor P.","family":"Pogribny","sequence":"additional","affiliation":[{"name":"National Center for Toxicological Research, U.S. Food and Drug Administration  Jefferson Arkansas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Rusyn","sequence":"additional","affiliation":[{"name":"Department of Environmental Sciences and Engineering, University of North Carolina  Chapel Hill North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,9,2]]},"reference":[{"key":"e_1_2_4_2_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-13-2107"},{"key":"e_1_2_4_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jviscsurg.2010.12.012"},{"key":"e_1_2_4_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00204-012-0931-2"},{"key":"e_1_2_4_5_1","first-page":"9","article-title":"Strain and species differences in susceptibility to liver tumour induction","volume":"51","author":"Bannasch P.","year":"1983","journal-title":"IARC Sci. 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