|
 |
|
EDRI Federal Project Inventory:
53887-05 Mechanism of Dioxin Action
- Sponsor Organization: NIH/NCI
- Project Title: 53887-05 MECHANISM OF DIOXIN ACTION
- Project Focus: EXPOSURE ASSESSMENT, HUMAN HEALTH EFFECTS
- Description: The long-term goal of this project is to understand the molecular
mechanism of 2,3,7,8-tetrachlorodibenzo-p-dioxin(TCDD, dioxin) action.
TCDD is a widespread, persistent environmental contaminant that, in
animals, producesmorphological, immunologic, biochemical, teratogenic,
and neoplastic effects. The risk that TCDD and relatedhalogenated
aromatic hydrocarbons pose to humans is unknown, with potential
reproductive and carcinogenic effectsbeing of most concern. The
induction of CYP1A1 gene transcription in mouse hepatoma cells is a
useful response foranalyzing the mechanism of dioxin action.
Increased gene expression requires the binding of TCDD to an
intracellularprotein (the Ah receptor), followed by the interaction of
the liganded receptor with a specific DNA recognitionsequence, which
is present in multiple copies within a transcriptional enhancer
located upstream of the CYP1A1I gene. The studies described in this
application are designed to analyze the mechanism of dioxin action in
greater depth. Theexperiments involve the use of molecular genetic
techniques to analyze (a) the structure and function of the dioxin-
responsive enhancer and CYP1A1I transcriptional promoter, (b) the TCDD
inducible, Ah receptor-dependent protein-DNA interactions at the
enhancer/promoter region within the intact cell, (c) the chromatin
structure of the CYP1A1 geneand the changes that occur in response to
TCDD, (d) the mechanism by which inhibition of protein
synthesissuperinduces CYP1A1 transcription, (e) the structure and
function of the Ah receptor, and (f) TCDD-inducible, Ahreceptor-
dependent transcription in vitro.
- References:
- Category: MODELS
- Subcategory: BASIC RESEARCH
- Keywords for Experimental System/Species: LABORATORY STUDY, IN VITRO
- Keywords for Experimental Endpoints: AH RECEPTOR, MOLECULAR, GENE EXPRESSION
- Chemical Agents: TCDDs (1746-01-6)
- Performing Institution: STANFORD UNIVERSITY
- Contact: CONTACT PERSON:ELAINE C. LEE; BUILDING 31; 11A21, NATIONAL CANCER
INSTITUTE, NIH,BETHESDA, MD 20892-2590; 301 496-5515;
LEEE@0D.NCI.NIH.GOV
|
|
