Abstract: The overall goal of this proposal is 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 EBO promotes oxidative damage of cellular DNA through formation of mutagenic hydroxyl radical (OH) -generated bases. Last year we published a study (Biochemistry, (2O00) 39:5474) that demonstrated activated leukocytes can 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 (8OHG), 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. The results of our initial studies identifying brominated bases by mass spectrometry were recently published (Biochemistry, (2001) 40:2041-2051) We are presently performing studies aimed at quantifying these EPO-specific brominated bases in a well- characterized repository of breast carcinoma and microscopically normal breast tissue specimens.
| Limitations: |
 APPROVED FOR PUBLIC RELEASE |
| Description: |
Annual rept. 1 Jul 2000-30 Jun 2001 |
| Pages: |
33 |
| Report Date: |
JUL 2001 |
| Contract Number: |
DAMD17-99-1-9133 |
| Report Number: |
A238693 |
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