Altered in vivo toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in c-src deficient mice

Fumio Matsumura, Essam Enan, Debra Y. Dunlap, Kent E Pinkerton, Janice Peake

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Abstract

Administration of a single i.p. dose of 115 μg/kg of 2,3,7,8- tetrachlorodibenzo-p-dioxin (TCDD) to homozygous and heterozygous c-src deficient mice (i.e. e-sre -/- and -/+ mice) and their wild-type littermates (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-src -/+ mice these effects were modest and were not statistically significant. Yet, hepatomegaly, a characteristic effect of TCDD, took place in all three strains of mice. Histological examination of liver samples from control mice and from mice treated with TCDD for 10 days showed that there are qualitative differences in the expression of the effects of TCDD between control and treated mice as well as between c-src -/+ and +/+ mice. In the case of c-src +/+ mice, the predominant lesions were lipid accumulation, glycogen depletion, edema formation and necrosis, as shown by the presence of large areas of ballooning degeneration, and cellular influx of fluid. These changes were demonstrated only marginally in c-src -/+ mice. The predominant effect in -/+ mice was edema formation. At a high dose of TCDD (345 μg/kg), all of the +/+ mice died within 34 days, whereas none of the c-src -/+ mice died. Together these results clearly indicate that some of the toxic effects of TCDD are not fully expressed in c-src deficient mice.

Original languageEnglish (US)
Pages (from-to)1397-1404
Number of pages8
JournalBiochemical Pharmacology
Volume53
Issue number10
DOIs
StatePublished - May 15 1997

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Keywords

  • C-src deficient mice
  • Qualitative difference in hepatotoxicity
  • Reduction of toxicity
  • TCDD

ASJC Scopus subject areas

  • Pharmacology

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