Dioxin and Organotin Compounds as Model Immunotoxic Chemicals

  • J. G. Vos
  • A. H. Penninks

Abstract

Studies in various animal models indicate that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin) and approximate isostereomers produce a similar pattern of toxic responses, including thymic atrophy. Effects on the immune system include suppression of cell-mediated immunity. Also in man, exposure to TCDD-related halo-genated aromatic hydrocarbons has been shown to impair thymus-dependent immunity. Several investigations have been performed to clarify the thymus atrophy. TCDD is not directly toxic for thymocytes, nor does it act through an increase of serum corticosteroid levels or a decrease of growth hormone levels. In studies with murine inbred strains differing in sensitivity to TCDD it has been shown that thymic atrophy segregates with the Ah locus and thus appears to be mediated by the Ah receptor. Recent studies indicate that TCDD acts through a receptor in thymic epithelium. Treatment of monolayers of thymic epithelial cells with TCDD resulted in the suppression of epithelium-dependent responsiveness of co-cultured thymocytes to mitogens. These results provide direct evidence that thymic epithelium is a target for TCDD. These findings are consistent with the hypothesis that TCDD stimulates terminal differentiation of reticular thymic epithelial cells to a stage at which they have lost their ability to support thymocyte maturation, thus leading to depletion of cortical thymocytes.

Keywords

Toxicity Biphenyl Corticosterone Toxicology Eosinophilia 

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© J. G. Vos and A. H. Penninks 1987

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  • J. G. Vos
  • A. H. Penninks

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