Immunosuppression without liver induction by subchronic exposure to 2,7-dichlorodibenzo- p-dioxin in adult female B6C3F1 mice

Abstract

The overall objective of this investigation was to begin to characterize the structure-activity relationship associated with dioxin-induced suppression of humoral immunity. Subchronic exposure (14 days) to 2,3,8,8-tetrachlorodibenzo- p-dioxin (TCDD), the prototype of the class, produced a suppression of the antibody responses to both sheep erythrocytes, a T-dependent antigen, and dinitrophenyl-Ficoll, a T-independent antigen. Surprisingly, similar results were observed with 2,7-dichlorodibenzo- p-dioxin (DCDD), a dioxin congener lacking affinity for the Ah receptor. In contrast, subchronic exposure to octachlorodibenzo- p-dioxin (OCDD), another dioxin congener without affinity for the Ah receptor, was devoid of activity. Subchronic exposure to 2,3,7,8-TCDD, but not 2,7-DCDD, produced an induction of several liver parameters including: liver weight, amount of microsomal protein, amount of cytochrome P-450, activity of aminopyrine- N-demethylase and activity of aryl hydrocarbon hydroxylase. Subchronic exposure to 2,3,7,8-TCDD or 2,7-DCDD produced no marked changes in thymus weight. Acute exposure to 2,3,7,8-TCDD also produced suppression of the antibody response in the absence of effects on the thymus.