Eosinophils as Mediators of DNA Oxidative Damage in Breast Cancer
Abstract
The overall goal of this proposal was to test the hypothesis that eosinophils promote DNA oxidative damage in breast carcinoma. DNA oxidative damage is linked to mutation, transformation and cancer development and eosinophil peroxidase (EPO), a hemoprotein secreted from eosinophils, is present in the majority of breast cancer biopsies. Our initial aim was to determine whether EPO promotes oxidative damage of cellular DNA through formation of mutagenic hydroxyl radical (OH) -generated bases. In a recent published study (Biochemistry, 39:5474) we show that activated leukocytes oxidatively damage DNA, RNA and the nucleotide pool through halide-dependent formation of OH. *OH-dependent damage of DNA was quantified by monitoring the content of 8-hydroxyguanine (SOHO), an established OH- specific DNA oxidation product that is mutagenic and implicated in breast cancer development and progression to metastatic disease. To test the hypothesis that EPO promotes DNA oxidative damage in human breast carcinoma, we have identified a family of novel brominated DNA oxidation products. These may serve as "molecular fingerprints" for DNA damage by the EPO pathway of eosinophils. We are presently developing GC/Ms methods to quantify these EPO-specific brominated bases in a well-characterized repository of breast carcinoma and microscopically normal breast tissue specimens.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2000
- Accession Number
- ADA384032
Entities
People
- Stanley Hazen