ABSTRACT
PURPOSE: To study the effect of epidermal growth factor (EGF) on the radiation sensitivity of MCF-7 breast cancer cells. METHODS AND MATERIALS: Radiation dose survival curves were generated for MCF-7 cells under conditions of hormonal deprivation. Epidermal growth factor and/or a monoclonal antibody to its receptor (mAb-225) were added prior to irradiation. Cell cycle distribution was determined by flow cytometry and cellular glutathione (GSH) levels were measured by a glutathione reductase assay. RESULTS: Under hormonal deprivation (control), more than 90% of the MCF-7 cells were arrested in G0/G1 phase and the D(o) of their survival curve was 0.66 +/- .01 Gy. The addition of EGF resulted in (a) growth stimulation; (b) increased percentage of cells in the S-phase of the cell cycle; (c) increased radioresistance (D(o) = 0.81 +/- .04 Gy; p < .05, compared with controls); (d) increased cellular GSH level. The EGF effect on radiation response was observed in a time- and dose-dependent manner. The addition of mAb-225 blocked the ability of EGF to enhance growth and radioresistance (D(o) = 0.68 +/- .03 Gy). CONCLUSION: Epidermal growth factor stimulates the growth and when administered prior to irradiation increases the radioresistance of hormone-deprived MCF-7 cells. These effects are inhibited by a specific antibody to the EGF receptor. Epidermal growth factor concomitantly increased the fraction of S-phase cells and intracellular GSH levels. This system of growth factor-altered radiosensitivity in human breast cancer cells provides a useful model for the study of the radiation response mechanisms in human malignancy.
