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 tried to develop 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 (CC/MS) analysis, but found that HPLC with electrochemical detection works, instead. The sample preparation and analytical methods have been developed, and we have made preliminary analyses of human breast tissue. These initial data indicate that women with breast cancer have more 4-hydroxyestrogens than 2-hydroxyestrogens and that methylation of CE is very poor. These results are consistent with the hypothesis guiding this research.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 1999
- Accession Number
- ADB251709
Entities
People
- Eleanor G. Rogan
Organizations
- University of Nebraska Medical Center