The N-nitrosodiethylamine mouse model: sketching a timeline of evolution of chemically-induced hepatic lesions

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.