The Effect of Radiotherapy Upon Primary Human Mammary Epithelial Cells Which Harbor a Breast Cancer Susceptibility Gene

The purpose of this work is to determine whether genomic instability following radiotherapy is increased in breast cells that harbor either a BRCA-1 mutation relative to cells which carry two normal copies of the gene. Therefore mammary epithelial cells from women at high risk for carrying either a BRCA-1 or BRCA-2 germline mutation were tested and two cell lines were found to harbor a germline mutation. These cells will be compared with mammary cells from women not at risk for carrying a mutation following radiation using the following assays: growth factor independence, growth in soft agar, and tumorigenicity in vivo. Radiation experiments using immortalization growth factor independence, and soft agar growth as endpoints have not identified any differences in genomic stability in the presence of a mutated gene. The final phase of this research, ie, injecting immuno deficient mice with irradiated mutated breast cells, has also not shown differences relative to irradiated wild-type cells.