A Modified Protocol of Diethylnitrosamine Administration in Mice to Model Hepatocellular Carcinoma
A Modified Protocol of Diethylnitrosamine Administration in Mice to Model Hepatocellular Carcinoma
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DOI：
10.3390/ijms21155461
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发表时间：
2020-08-01
影响因子：
5.6
通讯作者：
Lee, Woon Kyu
中科院分区：
文献类型：
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作者：
Memon, Azra;Pyao, Yuliya;Lee, Woon Kyu
我们的目的是建立一个肝细胞癌（HCC）的动物模型，具有较短的时间，高生存率，以及高发病率的肝癌在男性和女性比以前的报道。二乙基亚硝胺（DEN）模型具有年龄相关效应。单剂量的DEN治疗在50周的年轻小鼠中是不够的。在成人多次给药试验中，无论是否有促进剂，都显示出相同的模式。在这项研究中，两周龄的C57 BL 6小鼠被给予总共八个剂量的DEN，最初20 mg/kg体重，然后在第三周30 mg/kg，然后在最后六周50 mg/kg。第一组仅给予DEN治疗，其余两组在最后一次DEN治疗后休息一周后接受硫代乙酰胺（TAA）治疗4周或8周。在每组中DEN初始剂量24周后进行尸检。整个组中HCC的细胞排列是高分化癌，肿瘤存在对小鼠的存活没有显著影响。在所有肿瘤诱导组中，血清中生化标志物水平升高、组织结构丧失、肝细胞死亡和增殖均高度活化。这一发现证明了一种改进的策略，可以在短时间内生成肿瘤发生率高且合并肝硬化的动物模型，无论性别如何，都可以用于研究肝癌相关性的研究人员。
We aimed to create an animal model for hepatocellular carcinoma (HCC) with a short time, a high survival rate, as well as a high incidence of HCC in both males and females than previously reported. The Diethylnitrosamine (DEN) model has an age-related effect. A single dose of DEN treatment is not enough in young mice up to 50 weeks. The same pattern is shown in an adult with multiple-dose trials whether or not there is some promotion agent. In this study, two-week old C57BL6 mice were given a total of eight doses of DEN, initially 20mg/kg body weight, and then 30mg/kg in the third week, followed by 50mg/kg for the last six weeks. The first group is DEN treatment only and the other two groups received thioacetamide (TAA) treatment for four or eight weeks after one week of rest from the last DEN treatment. An autopsy was performed after 24 weeks of the initial dose of DEN in each group. The cellular arrangement of HCC in the entire group was well-differentiated carcinoma and tumor presence with no significant impact on the survival of mice. Increased levels of the biochemical markers in serum, loss of tissue architecture, hepatocyte death, and proliferation were highly activated in all tumor-induced groups. This finding demonstrates an improved strategy to generate an animal model with a high occurrence of tumors combined with cirrhosis in a short time regardless of sex for researchers who want to investigate liver cancer-related.