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Title: Species-specific recombinant cell lines as bioassay systems for the detection of 2,3,7,8-tetrachlorodibenzo-p-dioxin-like chemicals.

Authors: Garrison, P M; Tullis, K; Aarts, J M; Brouwer, A; Giesy, J P; Denison, M S

Published In Fundam Appl Toxicol, (1996 Apr)

Abstract: 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.

PubMed ID: 8812265 Exiting the NIEHS site

MeSH Terms: Animals; Biological Assay/methods; Cell Line; Humans; Luciferases/biosynthesis; Luciferases/genetics; Mice; Polychlorinated Biphenyls/pharmacology; Polychlorinated Dibenzodioxins/analogs & derivatives*; Polychlorinated Dibenzodioxins/analysis*; Receptors, Aryl Hydrocarbon/drug effects*; Receptors, Aryl Hydrocarbon/genetics; Receptors, Aryl Hydrocarbon/metabolism; Recombination, Genetic; Species Specificity; Transfection

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