Abstract

The long term goal of the project is to understand at the molecular level how the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces aryl hydrocarbon hydroxylase (AHH) activity in mammalian cells. The studies pertain to the mechanism of dioxin action, the control of cytochrome P1-450 gene expression, and the regulation of transcription of mammalian genes.
The specific aims are to analyze the mechanism of superinduction of AHH activity in mouse hepatoma cells and to analyze the regulation of other, non-cytochrome P1-450 genes under transcriptional control by TCDD. The experiments involve the use of molecular biological techniques for constructing recombinant DNA molecules, biochemical and genetic methods for analyzing the structure and function of these molecules, and the use of these molecules to study the control of gene expression in wild type and variant mouse hepatoma cells.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37CA032786-06
Application #
3482264
Study Section
Chemical Pathology Study Section (CPA)
Project Start
1983-05-01
Project End
1991-04-30
Budget Start
1988-05-01
Budget End
1989-04-30
Support Year
6
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
Stanford University
Department
Type
Schools of Medicine
DUNS #
800771545
City
Stanford
State
CA
Country
United States
Zip Code
94305

  Publications

Wen, L P; Koeiman, N; Whitlock Jr, J P (1990) Dioxin-inducible, Ah receptor-dependent transcription in vitro. Proc Natl Acad Sci U S A 87:8545-9
Elferink, C J; Whitlock Jr, J P (1990) 2,3,7,8-Tetrachlorodibenzo-p-dioxin-inducible, Ah receptor-mediated bending of enhancer DNA. J Biol Chem 265:5718-21
Whitlock Jr, J P; Denison, M S; Durrin, L K et al. (1989) Regulation of cytochrome P1-450 gene expression in mouse hepatoma cells by 2,3,7,8-tetrachlorodibenzo-p-dioxin. Drug Metab Rev 20:839-46
Durrin, L K; Whitlock Jr, J P (1989) 2,3,7,8-Tetrachlorodibenzo-p-dioxin-inducible aryl hydrocarbon receptor-mediated change in CYP1A1 chromatin structure occurs independently of transcription. Mol Cell Biol 9:5733-7
Fisher, J M; Jones, K W; Whitlock Jr, J P (1989) Activation of transcription as a general mechanism of 2,3,7,8-tetrachlorodibenzo-p-dioxin action. Mol Carcinog 1:216-21
Israel, D I; Estolano, M G; Galeazzi, D R et al. (1985) Superinduction of cytochrome P1-450 gene transcription by inhibition of protein synthesis in wild type and variant mouse hepatoma cells. J Biol Chem 260:5648-53
Jones, P B; Galeazzi, D R; Fisher, J M et al. (1985) Control of cytochrome P1-450 gene expression by dioxin. Science 227:1499-502