TOXICITY OF 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN (TCDD) TO THE HUMAN THYMUS AFTER IMPLANTATION IN SCID MICE

There are conflicting data with regard to the sensitivity of the human immune system to the toxic action of the highly toxic environmental p ollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). SCID mice engraft ed with human fetal thymus and liver tissue fragments (SCID-hu mice), which sustain normal human T cell differentiation in the thymus graft, were used to directly assess the sensitivity of the human thymus for TCDD. Wistar rats and SCID-hu mice were exposed to 1, 5, or 25 mu g TC DD/kg body weight. Histopathologic effects were evaluated for rat thym us and transplanted human thymus on Day 4 after exposure. The relative size of the cortex showed a dose-dependent decrease in both the norma l rat thymus and grafted human thymus (significant at 25 mu g/kg). SCI D-ra mice (SCID mice with a fetal rat thymus and liver graft) were use d as an intermediate model between the normal rat and SCID-hu mice, an d were exposed to the same dose levels of TCDD. However, 90% of the SC ID-ra mice developed a cutaneous graft-versus-host reaction, associate d with lymphodepletion of the rat thymus grafts, and hence a limited n umber of SCID-ra mice were available for evaluation of TCDD effects. T he data obtained in SCID-ra mice were in line with those in normal rat and grafted human thymus. In gas chromatography/ mass spectrometry an alysis, TCDD tissue concentrations in the normal rat thymus and grafte d human thymus were similar. We conclude that the human thymus serves as a target for TCDD, and that the human thymus and the Wistar rat thy mus display a comparable sensitivity to the toxic action of TCDD. (C) 1995 Academic Press, Inc.