The effects of acute exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin on glioma-specific cytotoxic T-cell activity in Fischer 344 rats

Abstract

2,3,7,8-Tetrachlorodibenzo- p-dioxin (TCDD) is one of the most potent environmental immunomodulating agents identified so far. Historically, mice have been used to model mammalian immunobiology and most of the data gathered on the immunotoxicity of TCDD has been obtained from studies with mice. However, rats have been used more extensively in lexicological research to establish human risk assessment criteria. A need exists, therefore, to develop a database using the rat model in immunotoxicology so that complete animal toxicity studies can be conducted. We have treated female Fischer 344 rats with a single i.p. dose of 0.3,3.0, or 30.0 μ/kg TCDD or corn oil vehicle and examined cytotoxic T-cell (CTL) activities 24 days following treatment. Syngeneic in vivo tumor-specific CTLs were generated that model cell-mediated immune reactions against neoplastically transformed self antigens. RT2, a virally-induced Fischer 344 rat glioma, and D74, a ethylnitrosurea-induced Fischer 344 rat glioma were used as targets. This immunological parameter was compared to body, thymic, and liver weights as well as liver ethoxyresorufin deethylase (EROD) activity on day 24 post-TCDD treatment. The results indicate that Fischer 344 rats are very sensitive to TCDD as indicated by severe thymic atrophy and EROD induction at all three doses. In contrast, CTL activity was only marginally affected by these same doses of TCDD with only a modest suppression noted at the highest dose. These results indicate that the CTL response in rats may not be useful in characterizing the effects of this xenobiotic on immunocompetence in the rat.