IFN-gamma prevents chemically induced hepatocellular carcinoma and preneoplastic lesions in liver independent of functional T-cells

Transgenic mice, which overexpress IFN-gamma in the liver, suffer from chronic hepatitis. Chronic hepatitis is believed to promote hepatocarcinogenesis.

To test whether IFN-gamma transgenic mice are more suscepitible for the development of liver cancer, we chemically induced hepatocarcinogenesis in IFN-gamma transgenic or non-transgenic mice by treatment with diethylnitrosamine (DEN), promoted by Phenobarbital (PB) for 24 weeks. To further clarify the role of T-cells, we reconstituted myeloablatively irradiated IFN-transgenic and non-transgenic mice with bone marrow from RAG(-/-) mice or from wildtype mice as control. After 24 or 48 weeks, the resulting neoplastic and preneoplastic lesions were determined and graded in altered foci, adenomas and hepatocellular carcinomas.

In contrast to non-transgenic mice, IFN-gamma transgenic mice, whether non-reconstituted or reconstituted with RAG(-/-) or wildtype bone marrow, showed a significantly diminished number of altered foci (p<0.004) and were completely protected from hepatocellular carcinoma (p<0.002).

In conclusion, IFN-gamma transgenic mice are less sensitive for chemically induced liver tumors than non-transgenic mice. Thus, IFN-gamma seems to protect from liver cancer despite its activity in inducing chronic hepatitis. This protection of IFN-gamma was not dependent on the presence of T-cells.