Abstract
The toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin [TCDD] and its bioisosteres involves binding to a specific TCDD [Ah] receptor, interaction of this complex with chromatin, and the ultimate production of a pleiotropic response. We have hypothesized that TCDD toxicity also involves the production of oxidative stress [OS], and phagocytic cell activation may be a source of reactive oxygen species [ROS] following TCDD exposure. Evidence is provided for the activation of peritoneal exudate cells [PEC] following exposure of rats to TCDD. Increases of 2.5- and 3-fold in ROS production by PEC were observed 24 hrs following treatment of female Sprague-Dawley rats with a single dose of 50 μg TCDD/kg, utilizing the iodonitrotetrazolium and cytochrome c [cyt-c] reduction assays, respectively. However, no increases in ROS production by isolated PEC were observed following in vitro incubation with 5, 25, 50, 100, 125 and 10,000 ng TCDD/ml of the assay medium using the nitroblue tetrazolium and cyt-c reduction assays. Phorbol myristate acetate was utilized as a positive control and resulted in a 3.5-fold increase in ROS production after a 15 min incubation with 3 × 106 PEC/ml at 37° C. PEC activation may contribute to OS following TCDD exposure, and the process may be receptor mediated.