title: Diethylnitrosamine (DEN)-induced carcinogenic liver injury in mice.
abstract: The toxic properties of various nitrosamines in animals and humans are well established. The parenteral or oral administration of the smallest quantities of diethylnitrosamine (DEN) or dimethylnitrosamine (DMN) results in severe liver damage. Most prominent are intense neutrophilic infiltration, extensive centrilobular haemorrhagic necrosis, bile duct proliferation, fibrosis, and bridging necrosis that ends in hepatocarcinogenesis. Due to the robustness of the induced hepatic alterations, the application of DEN in rodents has become an attractive experimental model for studies aimed at understanding the pathogenetic alterations underlying the formation of liver cancer, which represents one of the most common malignancies in humans worldwide. However, several studies have shown that the hepatocarcinogenic effects of nitrosamines might vary with the genetic background of the animals, their sex, their age, and other factors that might impact the outcome of experimentation. We present general guidelines for working with DEN, and a detailed protocol that allows the establishment of highly reproducible liver cancer in mice. The outcome of liver injury after the application of DEN in mice, as estimated by the formation of cirrhosis and cancer, appears to be a suitable animal model for the analysis of some aspects and processes that promote the pathogenesis of hepatocellular carcinoma in humans.
authors.affiliation: Institute for Laboratory Animal Science and Experimental Surgery, University Hospital, RWTH Aachen University, Aachen, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Tolba
authors.affiliation: Institute for Occupational and Social Medicine, RWTH Aachen University, Aachen, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Kraus
authors.affiliation: Department of Internal Medicine III, RWTH University Hospital Aachen, Aachen, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Liedtke
authors.affiliation: Institute of Experimental and Clinical Pharmacology and Toxicology, Department of Toxicology, Eberhard Karls University of Tübingen, Tübingen, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Schwarz
authors.affiliation: Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry, RWTH University Hospital Aachen, Aachen, Germany for the Transregional Collaborative Research Center 'Organ Fibrosis: From Mechanisms of Injury to Modulation of Disease' (SFB/TRR57) rweiskirchen@ukaachen.de.
authors.forename: R
authors.initials: R
authors.lastname: Weiskirchen
mesh_terms: D000818:Animals; D002274:Carcinogens, Environmental / Q000633:toxicity*; D004052:Diethylnitrosamine / Q000633:toxicity*; D004195:Disease Models, Animal; D017408:Guidelines as Topic; D006801:Humans; D007756:Laboratory Animal Science / Q000592:standards; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D051379:Mice
chemical_list: D002274:Carcinogens, Environmental; D004052:Diethylnitrosamine
keywords: cancer; cytochrome P450; diethylnitrosamine; hepatocellular carcinoma; liver