|
Abstract:
These studies examine the role estrogens play in the initiating events in cancer. We hypothesize that to develop cancer, one first must have DNA damage, which escapes normal repair and is set as a mutation in a critical gene. DNA damage can occur by direct damage to DNA by estrogen metabolites, as assayed in small oligonucleotides using MALDI-TOF mass spectrometry. Moreover, culturing cells in high, physiological levels of estradiol (E2, 0.35 micronM) or 4-OHE2 (0.18 micronM) results in detectable depurinating adducts in the estrogen receptor-positive human cell line T47D and in the estrogen receptor-negative cell line MDA MB-468. In addition, the repair of an oligo containing a stable adduct and an apurinic (AP) site or just an AP site, was assayed using cellular extracts from MCF-10A1 human breast cell line. The MCF-10A1 cell extracts repaired oligos containing both a stable adduct and an AP site, as well as an AP site alone. However, the relative amount of repair depended on the relative portions of the sites of damage.
| Limitations: |
 APPROVED FOR PUBLIC RELEASE |
| Description: |
Final rept. 12 May 1997-12 May 2000 |
| Pages: |
28 |
| Report Date: |
JUN 2000 |
| Contract Number: |
DAMD179717029 |
| Report Number: |
B945462 |
|
|
|
|
|
Keywords relating to this report:
Email This Abstract
