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), 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.
Garrison
P M
PM
Department of Environmental Toxicology, University of California, Davis 95616, USA.
Tullis
K
K
Aarts
J M
JM
Brouwer
A
A
Giesy
J P
JP
Denison
M S
MS
D000818:Animals; D001681:Biological Assay / Q000379:methods; D002460:Cell Line; D006801:Humans; D008156:Luciferases / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D011078:Polychlorinated Biphenyls / Q000494:pharmacology; D000072317:Polychlorinated Dibenzodioxins / Q000031:analogs & derivatives* / Q000032:analysis*; D018336:Receptors, Aryl Hydrocarbon / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D011995:Recombination, Genetic; D013045:Species Specificity; D014162:Transfection
D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D011078:Polychlorinated Biphenyls; D008156:Luciferases