SPECIES-SPECIFIC RECOMBINANT CELL-LINES AS BIOASSAY SYSTEMS FOR THE DETECTION OF 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN-LIKE CHEMICALS

Exposure to specific polychlorinated diaromatic hydrocarbons (PCDH), s uch as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin), produces a wide variety of species- and tissue-specific toxic and biological effe cts. Many of these responses are mediated by the Ah receptor (AhR) and are modulated by the interaction of the PCDH:AhR complex with its DNA recognition sequence (the dioxin-responsive element (DRE)). We have c onstructed a recombinant expression plasmid which contains the lucifer ase gene under TCDD-inducible control of several DREs and responds to TCDD-like chemicals with the induction of firefly luciferase. Stable t ransfection of this vector into various cell lines has produced a seri es of species-specific cell bioassay systems that respond to TCDD-like chemicals with the induction of luciferase in a time-, dose-, and AhR -dependent manner. In addition, these cell lines have been used to dem onstrate that 2,2',5,5'-tetrachlorobiphenyl can act as a species-speci fic AhR antagonist. Overall, these recombinant cell lines can be used for the detection and relative quantitation of AhR agonists/antagonist s in complex mixtures of environmental and biological samples, for ide ntification and characterization of novel AhR agonists, and for examin ation of species differences in PCDH responsiveness. (C) 1996 Society of Toxicology