Role of H-ras gene in chronic liver damage in mice, by using transgenic mice carrying a human c-H-ras protogene without mutations

Hepatic tumors including hepatocellular carcinoma were generated by carbon tetrachloride in transgenic mice carrying a human c-H-ras gene (rasH2 mice). RasH2 mice express 2 to 3 times more ras protein (ras p21) in the liver than do non-Tg mice. When carbon tetrachloride was administered, the rasH2 mice produced about 5 times as many hepatic tumors than did the non-transgenic mice. However, neither the 10-100 times higher ras p21 expression required for murine fibroblast transformation by itself nor the mutational activation of the H-ras gene was observed in carbon tetrachloride-induced hepatic tumors. These results show that H-ras proto-oncogene expression in the murine liver, even if it is not high enough to transform cells, also causes liver tumors when CCl⁴ are repeatedly given.