Determination of Catechol Estrogen Adducts by High-Performance Liquid Chromatography: Establishing Biomarkers for the Early Detection of Breast Cancer
Abstract
In order to better understand the role of estrogen metabolism as it relates to breast cancer etiology, a new analytical technique that can measure CE and CE-DNA adducts at low endogenous levels is being developed. This new technique is based on HPLC analysis of fluorescent probes specific for CE and CE-DNA adducts. Reaction of a,a-dibromomalonates occurs quickly with catechols, and this malonate system is being developed to produce fluorescent probes for HPLC analysis. Synthesis of bis-(9-methylenefluorenyl) a,a-dibromomalonate and its reaction with catechol and 4-OHE(1) produced fluorescent products whose emission was red-shifted from 315 to 455 nm. This red-shift was also accompanied by reduced quantum yield that limits the sensitivity of the fluorenyl malonate probe. This derivation was also analyzed by fluorescence line narrowing spectroscopy (FLNS) to see structural differences could be observed. FLNS showed that small changes in A ring environments of catechol and 4-OHE(1) could be detected. In order to increase the sensitivity of malonate derived CE, bis-(9-methyleneanthranyl) a,a-dibromomalonate was synthesized. Reaction of the anthranyl malonate probe with CE is ongoing. The long-term goal for developing this new analytical assay is the establishment of biomarkers for the early detection of breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2000
- Accession Number
- ADB266081
Entities
People
- Douglas E. Stack
Organizations
- University of Nebraska Omaha