Abstract

The environment is filled with compounds known to be either toxic or carcinogenic. It is therefore important to understand how organisms respond to these agents at the cellular and molecular level. It is known that induction of cytochrome P-450 and other cellular proteins is a major part in the response. These proteins are involved in the ultimate metabolism of the xenobiotic agent but paradoxically, often activate its toxic and carcinogenic potential. The goal of this proposal is to define the regulation of a set of genes which are induced by aryl hydrocarbons in mice. We plan to apply previously used recombinant DNA technologies to identify the level of regulation of several cytochrome P-450 proteins and to extend the analysis to include other hydrocarbon inducible genes. The precise localization and characterization of the regulatory elements associated with these inducible genes will then be possible using gene transfer of the identified genes into appropriate cell types. By comparing a set of similarly regulated genes, the mechanisms of hydrocarbon gene regulation may be determined.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA039553-03
Application #
3178672
Study Section
Chemical Pathology Study Section (CPA)
Project Start
1985-04-01
Project End
1988-03-31
Budget Start
1987-04-01
Budget End
1988-03-31
Support Year
3
Fiscal Year
1987
Total Cost
Indirect Cost

  Institution

Name
Albert Einstein College of Medicine
Department
Type
Schools of Medicine
DUNS #
009095365
City
Bronx
State
NY
Country
United States
Zip Code
10461

  Publications

Tardiff, J; Krauter, K S (1998) Divergent expression of alpha1-protease inhibitor genes in mouse and human. Nucleic Acids Res 26:3794-9
LeBlanc-Straceski, J M; Montgomery, K T; Kissel, H et al. (1994) Twenty-one polymorphic markers from human chromosome 12 for integration of genetic and physical maps. Genomics 19:341-9
Montgomery, K T; LeBlanc, J M; Tsai, P et al. (1993) Characterization of two chromosome 12 cosmid libraries and development of STSs from cosmids mapped by FISH. Genomics 17:682-93
Borriello, F; Krauter, K S (1991) Multiple murine alpha 1-protease inhibitor genes show unusual evolutionary divergence. Proc Natl Acad Sci U S A 88:9417-21
Silver, G; Krauter, K S (1990) Aryl hydrocarbon induction of rat cytochrome P-450d results from increased precursor RNA processing. Mol Cell Biol 10:6765-8
Borriello, F; Krauter, K S (1990) Reactive site polymorphism in the murine protease inhibitor gene family is delineated using a modification of the PCR reaction (PCR + 1). Nucleic Acids Res 18:5481-7
Montgomery, K T; Tardiff, J; Reid, L M et al. (1990) Negative and positive cis-acting elements control the expression of murine alpha 1-protease inhibitor genes. Mol Cell Biol 10:2625-37
Silver, G; Reid, L M; Krauter, K S (1990) Dexamethasone-mediated regulation of 3-methylcholanthrene-induced cytochrome P-450d mRNA accumulation in primary rat hepatocyte cultures. J Biol Chem 265:3134-8
Silver, G; Krauter, K S (1988) The Ah domain of the mouse. Induction of proteins by the carcinogen 3-methylcholanthrene. Biochem J 252:159-65
Silver, G; Krauter, K S (1988) Expression of cytochromes P-450c and P-450d mRNAs in cultured rat hepatocytes. 3-Methylcholanthrene induction is regulated primarily at the post-transcriptional level. J Biol Chem 263:11802-7

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