A Modified Protocol of Diethylnitrosamine Administration in Mice to Model Hepatocellular Carcinoma.

Azra Memon,Jung Il Lee,Yuliya Pyao,Yerin Jung,Woon Kyu Lee

doi:10.3390/ijms21155461

Abstract

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.

Highlights

Hepatocellular carcinoma (HCC) is one of the most aggressive clinical conditions with high malignancy, quick progression, and poor prognosis [1,2]
Hepatocellular carcinoma is a chronic liver disease that starts as fibrosis, leads to cirrhosis, and results in cancer
Throughout the experimental period, body weight in the control group progressively increased every time whereas body weight in all treatment groups increased slowly at first, decreased after the last injection of DEN which was again slowly recovered after two weeks of the last injection

Summary

Introduction

Hepatocellular carcinoma (HCC) is one of the most aggressive clinical conditions with high malignancy, quick progression, and poor prognosis [1,2]. Hepatocellular carcinoma is a chronic liver disease that starts as fibrosis, leads to cirrhosis, and results in cancer. The treatment of hepatocellular carcinoma is often complex as cirrhosis is the major clinical risk factor associated with 80% of people with HCC [3], and the potential for surgical resection is limited because of the risk of inducing postoperative liver failure. Experimental models are playing a significant role in the study of HCC [5]. Transgenic, or conditional knock-out experimental models are mainly used in the study of HCC development [6,7]. The application of DEN at different concentrations and to animals of different ages has variant efficacy and efficiency

Objectives

Methods

Results

Conclusion