THE EFFECTS OF 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN EXPOSURE IN PRIMARY RAT ASTROGLIA - IDENTIFICATION OF BIOCHEMICAL AND CELLULAR TARGETS

This paper reports the results from in vitro experiments utilizing vit al fluorescent probes and biochemical assays to examine the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) and related compou nds in primary rat astroglia in an effort to identify the cellular sit e(s) involved in toxicity. Application of 100 nM 2,3,7,8-TCDD, a stron g Ah receptor agonist resulted in altered astroglial intracellular Ca2 + a significant decrease in glutathione, a disrupted mitochondrial mem brane potential, a significant decrease in glutamine synthetase immuno reactivity and eventual loss of pH maintenance. In contrast, applicati on of 10 mu M 7,2,3,4-TCDD, a weak Ah receptor agonist, had no effect on any parameters measured. These findings, coupled with the identific ation of the 9-10S cytosolic Ah receptor in cultured rat astroglia, ar e consistent with typical structure-activity relationships observed fo r other Ah receptor mediated responses. However, the time course of th e Ca2+, as well as other responses observed in this study, suggest tha t the above effects may not necessarily involve the formation of the n uclear Ah receptor complex. (C) 1997 Inter Press, Inc.