Genetics of carbon tetrachloride-induced liver injury in mice. II. Multigenic regulation.

Mice from many different congenic inbred strains were given an intramuscular injection of carbon tetrachloride (CCl4) in olive oil to determine the genetic influences on induction of, and recovery from, liver damage. Liver and blood samples were taken at days 1, 4 and 7. The degree of necrosis and lymphoid infiltration appeared to be controlled, qualitatively and quantitatively, by both H-2-linked and Ah-linked genes. Strain differences were noted in the patterns of hepatocellular necrosis and the proportions of lymphoid, monocytic and other inflammatory cells which characterized the infiltrating population. Kinetic studies of F1 hybrids from matings between the susceptible BALB/cJ male parent and the resistant SJL/J female parent suggested that two dominant genetic influences play a major role in CCl4-induced liver damage. The gene contributed from the BALB/cJ parent affects the extent of liver necrosis and a second gene from SJL/J augments recovery. These results suggest, therefore, that the CCl4-induced liver damage and subsequent recovery are under multigenic control by H-2, Ah and possibly other genes.