Variation in the hepatotoxic effects of carbon disulphide between different strains of rat

The hepatotoxic effects of carbon disulphide have been investigated in an outbred (Porton) strain of rat and in 8 inbred strains. Carbon disulphide (1.38 mmoles/kg body weight) was administered intraperitoneally to rats which had been pretreated with phenobarbitone and starved. Livers were taken for analysis 24 h later. A considerable genetic variation in the response of rats to carbon disulphide was observed. The extent of centrilobular hydropic degeneration varied greatly between strains and was accompanied by a high incidence of focal coagulative necrosis in the most susceptible rats. Analysis of variance of the accompanying changes in liver weight and water content and in total liver cytochrome P450 content gave statistical confirmation of a strain effect in the response to carbon disulphide. Highly significant strain x treatment interactions for these parameters were attributable to changes after carbon disulphide treatment rather than variation between phenobarbitone pretreated starved controls. The experiments were repeated in two blocks, 3 months apart. Block effects and interactions were significant in some cases but were quantitatively small and did not obscure a ranking based on histological assessment. AGUS rats were least affected by carbon disulphide whereas PVG and LEW rats showed extensive liver damage. Other strains (WA, Porton, F344, BDIX, WAG) showed a gradation of response between these extremes.