Role of H-ras gene in chronic liver damage in mice. By using transgenic mice carrying a human C-H-ras proto-oncogene 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 CC1(4) are repeatedly given.
Tsunematsu
S
S
Department of Medicine, Kanagawa Dental College, Japan.
Saito
H
H
Sato
R
R
Morizane
T
T
Ishii
H
H
D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity; D006528:Carcinoma, Hepatocellular / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras; D006801:Humans; D008099:Liver / Q000473:pathology*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation; D000090063:Proto-Oncogene Mas; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D002251:Carbon Tetrachloride; D018631:ras Proteins