Cleavage/Repair and Signal Transduction Pathways in Irradiated Breast Tumor Cells
Abstract
This work has been directed towards developing an understanding of the molecular and signal-transduction events mediating growth arrest and cell death in breast tumor cells after exposure to ionizing radiation. Our findings that the breast tumor cell fails to undergo apoptotic cell death in response to irradiation (as well as in response to Adriamycin) have provided the incentive for developing approaches for radio sensitization (and chemosensitization) of the breast tumor cell by combining conventional chemotehrapy and radiotherapy with relatively nontoxic Vitamin D3 analogs. In addition, we have discovered that irradiation has the capacity to promote the uptake and expression of exogenous genes, a finding which is the basis for the development of strategies for the delivery of cytotoxic and apoptosis-promoting genes to both p53 wild-type and p53 mutated breast tumor cells. Finally, the possible role of p53 in enforcing the fidelity of double-strand break repair has been investigated in matched p53+ and p53-defective breast epithelial cells. Putative double-strand break misrepair events, induced by bleomycin and detected as HPRT mutations, have been analyzed at both the chromosomal level and the DNA sequence level. Chromosomal stability, delayed reproductive death, and radiation-induced apoptosis and cell cycle perturbations have been assessed in the mutant cells in an attempt to determine whether specific types of misrepair events were accompanied by changes in these responses.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2000
- Accession Number
- ADB268297
Entities
People
- David A. Gewirtz
Organizations
- Virginia Commonwealth University