Continuation of the Core component is proposed to serve as a centralized source of estrogen compounds, linker conjugates, treated and non-treated oligonucleotides and mouse skin treated with polycyclic aromatic hydrocarbons (PAH), and as a repository for all human tissue and urine samples to be used in all five research project. All of the necessary facilities and expertise for the Core are available in the Cavelieri-Rogan research groups or elsewhere in the Eppley Institute. In brief, the Core will provide catechol estrogens (CE), CE-Q, depurinating CE-DNA adducts and CE conjugates with glutathione (and its breakdown products in the mercapturic acid biosynthesis pathway, namely, cysteine and N- acetylcysteine) to Projects 1-5 as needed for experiments or as reference standards enzyme assays or analytical techniques.. The Core will also provide linker conjugates for development of monoclonal antibodies to Project 4. The Core will provide various oligonucleotides, either treated with PAH or CE-Q, or non-treated to Projects 3 and 5. In addition, the Core will serve as the repository for all human breast, prostate tissue and urine samples, procured at UNMC, the Mayo Clinic or NYU School of Medicine, and distribute them to Projects 1 and 2 as needed. The Core will provide high quality synthesized estrogen compounds for the five projects and is essential for he preparation of linker conjugates used in Project 4. More important will be the procurement, storage, cataloguing and distribution of human samples for the study of breast cancer (tissue and urine samples from UNMC and Mayo) and prostate cancer (tissue and urine samples from NYU).

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
2P01CA049210-12A1
Application #
6493955
Study Section
Project Start
1988-12-01
Project End
2006-06-30
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
12
Fiscal Year
2001
Total Cost
$168,689
Indirect Cost
Name
University of Nebraska Medical Center
Department
Type
DUNS #
City
Omaha
State
NE
Country
United States
Zip Code
68198
Cavalieri, Ercole; Saeed, Muhammad; Zahid, Muhammad et al. (2012) Mechanism of DNA depurination by carcinogens in relation to cancer initiation. IUBMB Life 64:169-79
Zahid, Muhammad; Saeed, Muhammad; Rogan, Eleanor G et al. (2010) Benzene and dopamine catechol quinones could initiate cancer or neurogenic disease. Free Radic Biol Med 48:318-24
Saeed, Muhammad; Rogan, Eleanor; Cavalieri, Ercole (2009) Mechanism of metabolic activation and DNA adduct formation by the human carcinogen diethylstilbestrol: the defining link to natural estrogens. Int J Cancer 124:1276-84
Saeed, Muhammad; Higginbotham, Sheila; Gaikwad, Nilesh et al. (2009) Depurinating naphthalene-DNA adducts in mouse skin related to cancer initiation. Free Radic Biol Med 47:1075-81
Gaikwad, Nilesh W; Yang, Li; Muti, Paola et al. (2008) The molecular etiology of breast cancer: evidence from biomarkers of risk. Int J Cancer 122:1949-57
Chakravarti, Dhrubajyoti; Venugopal, Divya; Mailander, Paula C et al. (2008) The role of polycyclic aromatic hydrocarbon-DNA adducts in inducing mutations in mouse skin. Mutat Res 649:161-78
Lu, Fang; Zahid, Muhammad; Wang, Cheng et al. (2008) Resveratrol prevents estrogen-DNA adduct formation and neoplastic transformation in MCF-10F cells. Cancer Prev Res (Phila Pa) 1:135-45
Zahid, Muhammad; Saeed, Muhammad; Lu, Fang et al. (2007) Inhibition of catechol-O-methyltransferase increases estrogen-DNA adduct formation. Free Radic Biol Med 43:1534-40
Gaikwad, Nilesh W; Rogan, Eleanor G; Cavalieri, Ercole L (2007) Evidence from ESI-MS for NQO1-catalyzed reduction of estrogen ortho-quinones. Free Radic Biol Med 43:1289-98
Zahid, Muhammad; Gaikwad, Nilesh W; Rogan, Eleanor G et al. (2007) Inhibition of depurinating estrogen-DNA adduct formation by natural compounds. Chem Res Toxicol 20:1947-53

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