Production of a novel recombinant cell line for use as a bioassay system for detection of 2,3,7,8-tetrachlorodibenzo-p-dioxin-like chemicals

M. H. El-Fouly, C. Richter, J. P. Giesy, M. S. Denison

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Exposure to specific halogenated aromatic hydrocarbons (HAHs), such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), can produce a wide variety of species- and tissue-specific toxic and biological effects. The presence of HAHs in environmental samples as complex mixtures has made it difficult to predict the biological and toxic potency of these chemicals. We have used aspects of the molecular mechanism of action of these chemicals to develop a species-specific bioassay system for detection of bioactive HAHs in complex mixtures. Here we describe construction and utilization of a recombinant expression vector that responds to these HAHs with the induction of an easily measurable gene product, heat-stable human placental alkaline phosphatase (PAP). This vector contains the PAP gene under TCDD-inducible control of four dioxin-responsive DNA enhancer elements. HAH-inducible expression of PAP from the recombinant vector occurs in a dose- and Ah-receptor-(AhR-) dependent manner. Stable transfection of this vector into mouse hepatoma cells has produced a novel cell line in which AhR-dependent induction of gene expression can easily be measured. This transfected cell line can readily be used for detection and relative quantitation of AhR agonists in complex mixtures of environmental and biological samples and for identification and characterization of novel AhR agonists.

Original languageEnglish (US)
Pages (from-to)1581-1588
Number of pages8
JournalEnvironmental Toxicology and Chemistry
Volume13
Issue number10
StatePublished - Oct 1994

Fingerprint

Halogenated Hydrocarbons
halogenated hydrocarbon
Aromatic Hydrocarbons
Bioassay
aromatic hydrocarbon
Biological Assay
dioxin
bioassay
Cells
Cell Line
Complex Mixtures
phosphatase
Poisons
Genes
Pharmacologic Actions
Dioxins
gene
Gene expression
gene expression
Transfection

Keywords

  • 2,3,7,8-Tetrachlorodibenzo-p-dioxin
  • Ah receptor
  • Dioxin
  • Halogenated hydrocarbons
  • TCDD

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis
  • Environmental Chemistry
  • Environmental Science(all)

Cite this

Production of a novel recombinant cell line for use as a bioassay system for detection of 2,3,7,8-tetrachlorodibenzo-p-dioxin-like chemicals. / El-Fouly, M. H.; Richter, C.; Giesy, J. P.; Denison, M. S.

In: Environmental Toxicology and Chemistry, Vol. 13, No. 10, 10.1994, p. 1581-1588.

Research output: Contribution to journalArticle

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