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

Journal Article · Sat Oct 01 00:00:00 EDT 1994 · Environmental Toxicology and Chemistry; (United States)

DOI:https://doi.org/10.1002/etc.5620131006· OSTI ID:6808904

El-Fouly, M H; Richter, C; Giesy, J P ^[1]; Denison, M S ^[2]

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1. Michigan State Univ., East Lansing, MI (United States)
2. Michigan State Univ., East Lansing, MI (United States). Dept. of Biochemistry Univ. of California, Davis, CA (United States). Dept. of Environmental Toxicology

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. The authors 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 they 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.

• OSTI ID: 6808904
• Journal Information: Environmental Toxicology and Chemistry; (United States), Journal Name: Environmental Toxicology and Chemistry; (United States) Vol. 13:10; ISSN 0730-7268; ISSN ETOCDK
• Country of Publication: United States
• Language: English

Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
BIOASSAY
BIOLOGICAL MODELS
DIOXIN
DNA
DOSE-RESPONSE RELATIONSHIPS
ENZYME INDUCTION
ENZYMES
ESTERASES
GENE REGULATION
HETEROCYCLIC COMPOUNDS
HYDROLASES
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
PHOSPHATASES
PROTEINS
RECOMBINANT DNA
SENSITIVITY
TUMOR CELLS