Rui M Gil Da Costa1, Nuno Paula-Santos2, Ana Faustino Rocha3, Aura Colaço4, Carlos Lopes5, Paula A Oliveira6. 1. 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. 2. 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. 3. Veterinary Sciences Dept., University of Trás-os-Montes and Alto Douro (UTAD), Vila Real, Portugal. 4. 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. 5. 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. 6. 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.
Abstract
BACKGROUND/AIM: 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. MATERIALS AND 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. CONCLUSION: Results allowed sketching of a timeline of evolution of DEN-induced hepatic lesions in mice, from initial lesions to malignant neoplasms. Copyright
BACKGROUND/AIM: 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. MATERIALS AND 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. CONCLUSION: Results allowed sketching of a timeline of evolution of DEN-induced hepatic lesions in mice, from initial lesions to malignant neoplasms. Copyright
Authors: Eva Moreno; Mathilda J M Toussaint; Saskia C van Essen; Laura Bongiovanni; Elsbeth A van Liere; Mirjam H Koster; Ruixue Yuan; Jan M van Deursen; Bart Westendorp; Alain de Bruin Journal: Hepatology Date: 2021-01 Impact factor: 17.425