Clear cell foci of altered hepatocytes and hepatocellular carcinomas in the N-Nitrosomorpholine (NNM) model in the rat show an overexpression of pro-oncogenic pathways and metabolic alterations similar to lesions in the islet-transplantation model

Abstract

Background and aims: Administration of the N-Nitrosamine N-Nitrosomorpholine (NNM) in rats is a well examined model of chemically induced hepatocarcinogenesis and starts with the formation of focal pre-neoplastic lesions in the liver, i.e. clear cell foci (CCF) of altered hepatocytes, and induces the formation of hepatocellular adenomas (HCA) and carcinomas (HCC). Similar lesions are known in the rat model of insulin-induced hepatocarcinogenesis and also in the human liver, which reveal an activation of the AKT/mTOR and Ras/MAPK pathways and the lipogenic phenotype, as we described previously.