We will study variants of the Hepa 1clc7 mouse hepatoma cell line which have markedly increased or decreased ability to metabolize the carcinogenic polycyclic aromatic hydrocarbon benzo(a)pyrene. We will characterize these variants with respect to their content of certain microsomal drug-metabolizing enzyme activities, their content of cytosolic Ah receptor, and their karyotype. We will use the fluorescence-activated cell sorter to assess heterogeneity in benzo(a)pyrene metabolism among the variants. We will construct molecules containing the DNA sequence for aromatic hydrocarbon-induced cytochrome P450 and DNA sequence for the cytosolic receptor, and we will use these probes to study the structure and function of these genes in the variants. These studies will increase our understanding of the control of carcinogen-metabolizing enzymes and the role which the Ah receptor plays in governing the activities of microsomal enzyme systems. They are relevant to health problems related to interindividual differences in drug metabolism and drug toxicity, drug interaction, and environmental carcinogenesis.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA032786-03
Application #
3170639
Study Section
Chemical Pathology Study Section (CPA)
Project Start
1983-05-01
Project End
1986-04-30
Budget Start
1985-05-01
Budget End
1986-04-30
Support Year
3
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Stanford University
Department
Type
Schools of Medicine
DUNS #
800771545
City
Stanford
State
CA
Country
United States
Zip Code
94305
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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
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