N-亚硝基二乙胺诱导的小鼠模型：化学诱导肝损伤的演变过程概述。
The N-nitrosodiethylamine mouse model: sketching a timeline of evolution of chemically-induced hepatic lesions.
机构信息
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.
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.
出版信息
Anticancer Res. 2014 Dec;34(12):7029-37.
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.
背景/目的：肝细胞癌（HCC）是一种常见且侵袭性强的恶性肿瘤，与多种环境危险因素有关。二乙基亚硝胺（DEN）诱导的小鼠模型为肝癌的发生提供了有用的见解，即 HCC。本研究旨在研究肝致癌作用的多步骤过程，为该主题的动物研究提供系统框架。
材料和方法
雄性 ICR 小鼠分为六组对照和六组 DEN 暴露组。分别连续腹腔内注射生理盐水和 DEN 溶液 8 周。在第一次给药后 8、15、22、29、36 和 40 周，两组（DEN 与对照）处死。
结果
在第 8 周及以后，发生了水样变性、坏死和凋亡。29 至 40 周时出现增生性病灶，伴有弥漫性发育不良区和肝细胞腺瘤。36 和 40 周还发现了肝血窦扩张。仅在 40 周时发现 HCC，显示出恶性肿瘤的特征性组织学特征。
结论
结果描绘了 DEN 诱导的小鼠肝损伤从初始损伤到恶性肿瘤的演变时间表。
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