CHARACTERIZATION OF THE EFFECTS OF 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN IN B6C3F1 AND DBA 2 MICE FOLLOWING SINGLE AND REPEATED EXPOSURES/

Previous studies have demonstrated that repeated (14 day) administrati on of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) enhances the suppress ion of humoral immunity in DBA/2 (Ah-low responder) mice relative to t he effect seen with identical cumulative doses after a single treatmen t (cumulative doses of 4.3, 14.0, and 42 mg/kg). In the present studie s, we have explored this phenomenon further by determining the status of several specific parameters, which might account for the increase i n antibody suppression in the DBA/2 strain following repeated TCDD exp osures. Included in these studies was the induction of hepatic and spl enic microsomal 7-ethoxyresorufin-o-deethylase (EROD; P4501A1) activit y and biodistribution of the administered TCDD into various target org ans and tissues. Changes in lymphocyte subpopulations within the splee n were also assessed by flow cytometry following both single and repea ted dosing. All studies made use of direct comparisons between DBA/2 ( Ah-low responder) and B6C3F1 (Ah-high responder) female mice. Results of these studies demonstrate that the enhanced suppression of humoral immunity in DBA/2 mice following repeated exposure to TCDD is not dire ctly associated with increases in liver microsomal EROD activity and d oes not appear to be correlated with changes in the pattern of biodist ribution or amount of TCDD within the liver or spleen of these animals . In contrast, the most significant changes that occurred following re peated dosing in either strain were observed in the levels of microsom al EROD activity and immune cell ratios within the spleen. This effect was characterized as an increase in microsomal EROD activity, and a c orresponding reduction in the numbers of a non-B/non-T cell population in the spleen.