The Failure of Repair Enzymes in the Catechol Estrogen-Induced DNA Damage as Potential Initiating Event in Human Breast Cancer
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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2000
- Accession Number
- ADB264549
Entities
People
- Eleanor G. Rogan
- Kimberly Chapman
Organizations
- University of Nebraska Medical Center