We describe novel photochemical and enzymatic methods for mapping drug and carcinogen binding sites on DNA. We propose to use those methods to develop rules for predicting benzo(a)pyrene-diol-epoxide (BPDE) binding sites on eukaryotic genes. As a class, we propose to use the photochemical methods as tools to explore the relation between DNA sequence and DNA structure in the chicken Beta A globin gene, and in the SV40 enhancer/origin of replication. In a separate set of BPDE binding experiments we will determine if the c-myc oncogene contains high affinity carcinogen binding sites and will map the distribution of BPDE molecules within such regions at one base resolution. We also describe methods for mapping BPDE binding to oncogenes in intact nuclei. The goal of these experiments is to determine if, in a mouse B cell, the c-myc gene is involved in chemical carcinogenesis because the gene is sensitive to attack by an environmental toxin. We also propose to map BPDE binding sites on the myc gene in BALB/c-3T3 cells. The goal of those experiments is to determine if carcinogen binding to an oncogene shows cell specific differences.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA039527-02
Application #
3178598
Study Section
Chemical Pathology Study Section (CPA)
Project Start
1985-04-01
Project End
1988-03-31
Budget Start
1986-04-01
Budget End
1987-03-31
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Princeton University
Department
Type
Schools of Arts and Sciences
DUNS #
002484665
City
Princeton
State
NJ
Country
United States
Zip Code
08544
Chan, S S; Breslauer, K J; Hogan, M E et al. (1990) Physical studies of DNA premelting equilibria in duplexes with and without homo dA.dT tracts: correlations with DNA bending. Biochemistry 29:6161-71
Boles, T C; Hogan, M E (1987) DNA structure equilibria in the human c-myc gene. Biochemistry 26:367-76