ALTERED IN-VIVO TOXICITY OF 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN (TCDD) IN C-SRC DEFICIENT MICE

Administration of a single i.p. dose of 115 mu g/kg of 2,3,7,8-tetrach lorodibenzo-p-dioxin (TCDD) to homozygous and heterozygous c-src defic ient mice (i.e. c-src -/- and -/+ mice) and their wild-type littermate s (c-src +/+ mice) induced differential toxic responses. In c-src +/mice, there were clear-cut signs of the toxicity of TCDD, such as the loss of weight in the body, thymus and adipose tissue, whereas in c-sr c -/+ mice these effects were modest and were not statistically signif icant. Yet, hepatomegaly, a characteristic effect of TCDD, took place in all three strains of mice. Histological examination of liver sample s from control mice and from mice treated with TCDD for 10 days showed that there are qualitative differences in the expression of the effec ts of TCDD between control and treated mice as well as between c-src - /+ and +/+ mice. In the case of c-src +/+ mice, the predominant lesion s were lipid accumulation, glycogen depletion, edema formation and nec rosis, as shown by the presence of large areas of ballooning degenerat ion, and cellular influx of fluid. These changes were demonstrated onl y marginally in c-src -/+ mice. The predominant effect in -/+ mice was edema formation. At a high dose of TCDD (345 mu g/kg), all of the +/ mice died within 34 days, whereas none of the c-src -/+ mice died. To gether these results clearly indicate that some of the toxic effects o f TCDD are not fully expressed in c-src deficient mice. (C) 1997 Elsev ier Science Inc.