Determination of Catechol Estrogen Adducts by High-Performance Liquid Chromatography: Establishing Biomarkers for the Early Detection of Breast Cancer

Abstract

The metabolism of estrogen produces reactive electrophiles, catechol estrogen quinones (CE-Q). CE-Q have been shown to be genotoxic, reacting with DNA to produce CE-DNA adducts. In order to determine the correlation between formation of CE-Q and breast cancer, an analytical protocol that can measure CE-DNA adducts at ultra-low, endogenous levels in breast tissue is being developed. The synthesis of novel fluorescent probes specific to the catechol moiety was the focus of this year's work. These fluorescent probes will allow HPLC analysis of CE metabolites and CE-DNA adducts at the femtamolar level. Starting from anthracene, dichloro-di-(9-anthryl)methane was synthesized in three steps. The dibromo analog is also under production. In addition, probes base on flurocene have been generated so that derivation of catechol structures leads to a sprio ring system. The production of a sprio ring system was also explored using the commercially available dichlorodiphenylsilane. The synthesis of gram quantities of 4-hydroxyestrone and 4- hydroxyestradiol was also accomplished in year 1. The ultimate goal of this research is the development of a biomarker for the early detection of breast cancer.

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Document Details

Document Type
Technical Report
Publication Date
Jul 01, 1999
Accession Number
ADB257200

Entities

People

  • Douglas E. Stack

Organizations

  • University of Nebraska Omaha

Tags

DTIC Thesaurus Topics

  • Biological Markers
  • Biomedical Research
  • Breast Cancer
  • Capillary Electrophoresis
  • Chemistry
  • Chromatography
  • Detection
  • Estrogens
  • Fluorescence
  • Government Procurement
  • Governments
  • Health Services
  • Liquid Chromatography
  • Mammary Glands
  • Medical Personnel
  • Metabolites
  • Neoplasms

Fields of Study

  • Chemistry

Readers

  • Analytical Chemistry
  • Molecular and genetic basis of cancer.
  • Organic Chemistry