Strain differences in mice in carbon tetrachloride-induced liver injury

A study was made in inbred mice of genetic determinants of toxic liver cell injury, and the subsequent occurrence of autoantibodies to mouse liver-specific protein (M-LSP). Carbon tetrachloride was injected s.c. in sublethal doses to induce liver cell damage in 4 strains of mice, BALB/c, C3H, C57BL/6 and SJL/J. The degree of liver cell damage was assessed by blood cholylglycine levels and by semiquantitative histological analysis 1, 4, 7, 14, 21 and 45 days after dosing. Striking differences were observed among the 4 strains in degrees of liver necrosis, cellular infiltration and rate of removal of the necrotic tissue. BALB/c was the strain most susceptible to the necrotizing effects of CCl4. These mice showed confluent areas of hepatocellular necrosis from Day 1 and histological recovery was protracted up to 3 weeks, and was accompanied by pronounced macrophage activity and a cellular inflammatory response. Mice of the SJL/J strain were the least susceptible and showed minor hepatocellular necrosis, which resolved by Day 7, and a slight histiocytic response. C3H and C57BL/6 showed lesions which were intermediate between the other 2 strains. The autoantibody response to LSP was weak, transient and detected only in C57BL/6 mice. This study indicates the presence of genetic control, either H-2 or non-H-2 linked, over the degree of liver cell necrosis resulting from toxic liver injury, and the ensuing cellular infiltrate and rate of removal of the necrotic tissue.