DNA Cleavage/Repair and Signal Transduction Pathways in Irradiated Breast Tumor Cells.
Abstract
These studies were designed to understand the role of c-myc and the p53 protein in the pathway leading to growth arrest in the breast tumor cell and in the relative refractoriness of breast tumor cells to the induction of apoptotic cell death. An additional component of this work was to investigate the repair of double-strand breaks induced by ionizing radiation (and by the radiomimetic, bleomycin) in breast tumor cells having wild-type versus mutant p53 genes and the relationship of double-strand break repair to apoptotic cell death. We have determined that radiosensitivity does not appear to be a function of p53 in breast tumor cells which fail to undergo apoptotic cell death and that suppression of c-myc may be a component of the signal transduction pathway leading to growth arrest in response to radiation only in p53 positive breast tumor cells. We have also determined that ionizing radiation fails to suppress the activity of the transcription factor E2F in breast tumor cells, suggesting the existence of a previously unidentified mechanisms for loss of restriction point control in the breast tumor cell. Finally, preliminary studies indicate that acquisition of a pleiotropic phenotype incorporating genomic instability and delayed reproductive death may be linked to mutagenesis induced by radiomimetic agents in 184B5 breast epithelial cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1997
- Accession Number
- ADA336577
Entities
People
- David Gewtrtz
Organizations
- Virginia Commonwealth University