Abstract

The complexes of carcinogens (e.g., benzo(a)pyrene, 4-nitro-quinoline-1-oxide, and acetoxy-acetylaminofluorene) with high molecular weight native DNA, plasmid DNA; synthetic DNAs, and deoxyoligonucleotides will be studied. The experiments will include Nuclear Magnetic Resonance (NMR), fluorescence, circular dichroism, and UV-Vis spectroscopic studies on the complexes of carcinogens with DNA and oligonucleotides. Of particular interest will be the structure of the complexes as well as the site-selectivity and cooperativity in the covalent binding of the carcinogens to DNA.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA035251-03
Application #
3172859
Study Section
Chemical Pathology Study Section (CPA)
Project Start
1983-08-01
Project End
1986-07-31
Budget Start
1985-08-01
Budget End
1986-07-31
Support Year
3
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
University of Rochester
Department
Type
Schools of Arts and Sciences
DUNS #
208469486
City
Rochester
State
NY
Country
United States
Zip Code
14627

  Publications

Rockwell, S; Knisely, J P (1997) Hypoxia and angiogenesis in experimental tumor models: therapeutic implications. EXS 79:335-60
Fountain, M A; Krugh, T R (1995) Structural characterization of a (+)-trans-anti-benzo[a]pyrene-DNA adduct using NMR, restrained energy minimization, and molecular dynamics. Biochemistry 34:3152-61
Eckel, L M; Krugh, T R (1994) Structural characterization of two interchangeable conformations of a 2-aminofluorene-modified DNA oligomer by NMR and energy minimization. Biochemistry 33:13611-24
O'Handley, S F; Sanford, D G; Xu, R et al. (1993) Structural characterization of an N-acetyl-2-aminofluorene (AAF) modified DNA oligomer by NMR, energy minimization, and molecular dynamics. Biochemistry 32:2481-97
Dittrich, K A; Krugh, T R (1991) Analysis of site-specific binding of (+/-)-anti-benzo[a]pyrene diol epoxide to restriction fragments of pBR322 DNA via photochemical mapping. Chem Res Toxicol 4:270-6
Dittrich, K A; Krugh, T R (1991) Mapping of (+/-)-anti-benzo[a]pyrene diol epoxide adducts to human c-Ha-ras1 protooncogene. Chem Res Toxicol 4:277-81
Huang, G J; Krugh, T R (1990) Large-scale purification of synthetic oligonucleotides and carcinogen-modified oligodeoxynucleotides on a reverse-phase polystyrene (PRP-1) column. Anal Biochem 190:21-5
Krugh, T R; Graves, D E; Stone, M P (1989) Two-dimensional NMR studies on the anthramycin-d(ATGCAT)2 adduct. Biochemistry 28:9988-94
Rockwell, S (1989) Tumor radiation responses and tumor oxygenation in aging mice. Exp Gerontol 24:37-48
Rosenberg, L S; Carvlin, M J; Krugh, T R (1986) The antitumor agent mitoxantrone binds cooperatively to DNA: evidence for heterogeneity in DNA conformation. Biochemistry 25:1002-8

Showing the most recent 10 out of 16 publications