Resistance against the development of diethylnitrosamine-induced hepatocellular carcinoma in female C3H mice: an experimental model

Abstract

Histopathological features of hepatocellular carcinoma (HCC) induced by diethylnitrosamine (DEN) in mice display strong similarities with those seen in humans, including the higher tumor prevalence in males than in females. Previous studies have demonstrated that continual production of the pro-inflammatory IL-6 by Kupffer cells is involved in the initiation and progression of DEN-induced HCC and that estrogen-mediated reduction of IL-6 secretion would decrease its incidence in females. Given the predominant utilization of male mice in hepatic carcinogenesis research, the objective of this study was to examine histopathological and immunological parameters in the DEN-induced liver carcinogenesis model in female C3H mice. We observed a significant prevalence of hepatocellular hyperplasias and adenomas alongside a minimal infiltration of inflammatory cells and a scarcity of senescent areas in females. Further, a low expression of immunosuppression markers is observed in females − such as neutrophil/lymphocyte ratio, PD-1 expression in CD8 T cells, and PD-L1 in myeloid cells − compared to males. Comparative studies between susceptible and resistant hosts to chemical carcinogenesis may help to unveil novel therapeutic strategies against cancer.