title: The N-nitrosodiethylamine mouse model: sketching a timeline of evolution of chemically-induced hepatic lesions.
abstract: OBJECTIVE
  Hepatocellular carcinoma (HCC) is a frequent and aggressive malignancy associated with multiple environmental risk factors. The chemically-induced mouse model of diethylnitrosamine (DEN) provides useful insight into liver carcinogenesis, namely HCC. This work aimed to study the multistep process of hepato-carcinogenesis, providing a systematic framework for animal studies on this subject.
  
  
  METHODS
  Male ICR mice were divided into six control and six DEN-exposed groups. Saline solution and DEN were injected intra-peritoneally, respectively, for eight consecutive weeks. Two groups (DEN vs. control) were euthanized at 8, 15, 22, 29, 36 and 40 weeks after the first administration.
  
  
  RESULTS
  Hydropic degeneration, necrosis and apoptosis were acutely induced at eight weeks and onwards. Hyperplastic foci occurred at 29 to 40 weeks along with diffuse dysplastic areas and hepatocellular adenoma. Peliosis hepatis were also identified at 36 and 40 weeks. HCC were only noted at 40 weeks, showing characteristic histological features of malignancy.
  
  
  CONCLUSIONS
  Results allowed sketching of a timeline of evolution of DEN-induced hepatic lesions in mice, from initial lesions to malignant neoplasms.
authors.affiliation: Laboratory for Process Engineering, Environment, Biotechnology and Energy (LEPABE), Chemical Engineering Department, Faculty of Engineering, University of Porto (FEUP), Porto, Portugal Experimental Pathology and Therapeutics Group, CI-IPOP, Portuguese Institute of Oncology, Porto, Portugal.
authors.forename: Rui M Gil
authors.initials: RM
authors.lastname: Da Costa
authors.affiliation: Veterinary Sciences Dept., University of Trás-os-Montes and Alto Douro (UTAD), Vila Real, Portugal Center for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), University of Trás-os-Montes and Alto Douro, Vila Real, Portugal.
authors.forename: Nuno
authors.initials: N
authors.lastname: Paula-Santos
authors.affiliation: Veterinary Sciences Dept., University of Trás-os-Montes and Alto Douro (UTAD), Vila Real, Portugal.
authors.forename: Ana Faustino
authors.initials: AF
authors.lastname: Rocha
authors.affiliation: Veterinary Sciences Dept., University of Trás-os-Montes and Alto Douro (UTAD), Vila Real, Portugal Veterinary and Animal Science Research Center (CECAV), Veterinary Science Department, University of Trás-os-Montes and Alto Douro (UTAD), Vila Real, Portugal.
authors.forename: Aura
authors.initials: A
authors.lastname: Colaço
authors.affiliation: Experimental Pathology and Therapeutics Group, CI-IPOP, Portuguese Institute of Oncology, Porto, Portugal Department of Pathology and Molecular Immunology, Abel Salazar Institute for Biomedical Sciences - University of Porto (ICBAS-UP), Porto, Portugal.
authors.forename: Carlos
authors.initials: C
authors.lastname: Lopes
authors.affiliation: Veterinary Sciences Dept., University of Trás-os-Montes and Alto Douro (UTAD), Vila Real, Portugal Center for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), University of Trás-os-Montes and Alto Douro, Vila Real, Portugal Center for the Study of Animal Sciences (CECA), Food and Agrarian Sciences and Technologies Institute (ICETA), University of Porto, Vairão, Portugal pamo@utad.pt.
authors.forename: Paula A
authors.initials: PA
authors.lastname: Oliveira
mesh_terms: D000477:Alkylating Agents / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D063646:Carcinogenesis / Q000139:chemically induced / Q000473:pathology*; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced* / Q000473:pathology; D004052:Diethylnitrosamine / Q000494:pharmacology*; D004195:Disease Models, Animal; D008099:Liver / Q000293:injuries / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010382:Peliosis Hepatis / Q000139:chemically induced; D011230:Precancerous Conditions / Q000473:pathology
chemical_list: D000477:Alkylating Agents; D004052:Diethylnitrosamine
keywords: N-Nitrosodiethylamine (DEN); carcinogenesis; hepatic lesions; histology; mice