Diethylnitrosamine-induced liver tumorigenesis in mice.

Abstract

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the third leading cause of cancer related mortality with a 10 year survival rate of merely 22-35%. Tumorigenesis frequently occurs in patients with chronic liver disease where continued liver cell damage, compensatory proliferation and inflammation provide the basis for tumor initiation, promotion and progression. Animal models of HCC are particularly useful to better understand molecular events underlying liver tumorigenesis. To this end, chemical carcinogenesis protocols based on the injection of genotoxic compounds such as diethylnitrosamine (DEN) are widely used to model liver tumorigenesis in rodents. DEN injection into 2 week old mice is sufficient to cause liver tumorigenesis after 8-10 months. When injected into older mice, DEN has to be combined with administration of tumor promoting agents such as phenobarbital or feeding high fat diet. Such protocols allow to dissect the different steps of tumor formation (i.e., tumor initiation and promotion) experimentally and to model liver pathologies in mice which frequently lead to HCC in human patients such as non-alcoholic fatty liver disease. Here, we review several established chemical carcinogenesis protocols based on DEN injection into mice and discuss their advantages as well as potential limitations.