© 1996 Oxford University Press
research-article |
Species-Specific Recombinant Cell Lines as Bioassay Systems for the Detection of 2,3,7,8-Tetrachlorodibenzo-p-dioxin-like Chemicals
*Department of Environmental Toxicology, University of California Davis, California 95616
Department of Toxicology, Agricultural University Wageningen, The Netherlands
Fisheries and Wildlife, Pesticide Research Center and Institute for Enviromnental Toxicology, Michigan State University East Lansing, Michigan 48824-1222
Received May 17, 1995; accepted October 6, 1995
Exposure to specific polychlorinated diaromatic hydrocarbons (PCDH), such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin), produces a wide variety of species- and tissue-specific toxic and biological effects. 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 constructed a recombinant expression plasmid which contains the luciferase gene under TCDD-inducible control of several DREs and responds to TCDD-like chemicals with the induction of firefly luciferase. Stable transfection of this vector into various cell lines has produced a series 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 demonstrate that 2,2',5,5'-tetrachlorobiphenyl can act as a species-specific AhR antagonist. Overall, these recombinant cell lines can be used for the detection and relative quantitation of AhR agonists/antagonists in complex mixtures of environmental and biological samples, for identification and characterization of novel AhR agonists, and for examination of species differences in PCDH responsiveness.