Genetics of liver tumor susceptibility in mice

A good experimental model of genetic predisposition to hepatocellular tumors is the murine strain C3H. These tumors share morphologic similarities with human hepatocellular tumors. After a treatment with a single small dose of chemical carcinogen, the C3H mice show a high susceptibility to the growth of hepatocellular neoplastic lesions, that reach a volume >100-fold as compared to the corresponding lesions of genetically resistant strains. Genetic linkage analysis experiments were conducted in 2 different crosses, with the C3H as one of the parental strains, and the other parental strains being represented by mice genetically resistant to hepatocarcinogenesis (A/J, M. spretus). Six different regions, on chromosomes 2, 5, 7, 8, 12, and 19 showed a significant linkage with hepatocellular tumor development. These results provide the genetic basis for the strain variations seen in susceptibility to hepatocarcinogenesis, indicating polygenic inheritance of this trait.