DNA Base Excision Repair (BER) and Cancer Gene Therapy: Use of the Human N-mythlpurien DNA Glycosylase (MPG) to Sensitize Breast Cancer Cells to Low Dose Chemotherapy
Abstract
The DNA Base Excision Repair (PER) pathway is responsible for the repair of alkylation and oxidative DNA damage resulting in protection against the deleterious effects of endogenous and exogenous agents encountered on a daily basis. The first enzyme in the human DNA PER pathway, N-methylpurine DNA glycosylase (MPG), is the focus of this proposal. This enzyme is responsible for the removal of damaged bases from the DNA resulting in an abasic site. Our laboratory has found that the overexpression of this DNA repair protein is cytotoxic to tumor cells in response to the classic alkylating agent, methyl methanesulfonate (MMS) It will be interesting to further investigate the use of MPG constructs to kill breast cancer cells in response to clinically relevant drugs used in breast cancer treatment protocols, such as thiotepa and cytoxan (cyclophosphamide) . Gene transfer of MPG could result in increased kill of breast cancer cells using lower doses of chemotherapy, therefore minimizing peripheral damage and eliminating the need for bone marrow rescue or transplant. This is particularly important in advanced stage (IV) treatments currently using high dose chemotherapy and bone marrow transplants.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2003
- Accession Number
- ADA416689
Entities
People
- Mark R. Kelly
- Tia Harvey
Organizations
- Indiana University