Initiation of Breast Cancer: Activated Catechol Estrogens.
Abstract
Determination of the levels of catechol estrogens (CE) in breast tissue constitutes important evidence for the hypothesis that human breast cancer and certain other cancers are initiated by activation of CE to CE- 3,4-quinones (CE-3,4-Q), which form depurinating DNA adducts. Apurinic sites generated by loss of the depurinating adducts can produce oncogenic mutations. Because only nonmethylated CE can be oxidized to CE-Q, the ratio of nonmethylated vs methylated CE should be higher and/or the level of catechol-O- methyltransferase (COMT) in breast tissue lower in women with breast cancer compared to women without disease. Our assays focus particularly on the 4-hydroxyestrogens and 4-hydroxy COMT. We are developing an assay to determine the levels of CE in breast tissue from pre- and post-menopausal women with and without breast cancer by gas chromatography/mass spectrometry (GC/MS) analysis. The GC/MS methods have been developed, and we are working to optimize the extraction of CE from mammary tissue. At the end of this grant we expect to have collected sufficient data on the levels of CE in breast tissue to make preliminary comparisons of women with and without breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 1998
- Accession Number
- ADA351950
Entities
People
- Eleanor G. Rogan
Organizations
- University of Nebraska Medical Center