The Failure of Repair Enzymes in the Catechol Estrogen-Induced DNA Damage as Potential Initiating Event.
Abstract
Endogenous carcinogens, cancer-causing agents formed in mammalian cells, have been poorly investigated. Our group has hypothesized and furnished evidence that oxidized metabolites of catechol estrogens (CE) initiate breast cancer by damaging DNA in breast cells. These active metabolites, the quinones of CE (CE-Q), bind to DNA and form two types of adducts: depurinating adducts that generate apurinic sites, and stable adducts that remain linked to DNA. It is logical to speculate that for the progression from DNA damage to mutation, the repair mechanisms within cells must sometimes fail. The main objective of these experiments is to demonstrate CE-Q-induced DNA damage and to shed light on the mechanism of faulty repair. First I have determined the level of DNA damage by CE and the cell type which underwent this damage by use of an unscheduled DNA synthesis assay in ACI rat mammary gland organ culture. Then, I have tried to design molecular biological techniques that display DNA damage. The most successful technique uses a series of radiolabeled single-strand oligonucleotides which contain a single site that can undergo CE-induced DNA damage creating strand breaks that are visualized on a polyacrylamide gel.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 1998
- Accession Number
- ADA352366
Entities
People
- Kimberly A. Chapman
Organizations
- University of Nebraska Omaha