PNNL

Abstract

Purpose: To investigate the magnitude and kinetics of shedding of epidermal growth factor (EGF) by human mammary epithelial cells (HMEC) in response to gamma irradiation in the 1-5 cGy dose range. Results: A biphasic dose response of radiation-induced shedding was observed with the greatest rate of shedding at 2.5 cGy. In the presence of antibodies that blocked the EFG receptor, EGF in the growth medium increased steadily for 2 hr post radiation exposure. A model for this sustained release of cytokines was developed based on delayed coupling between prompt activation of mitogen-activated-protein-kinase (MAPK) pathways and protease activity. The model fit to experimental data predicted time-dependent shedding with a maximum value about 150 min post exposure. After a 2.5 cGy exposure, the maximum rate of shedding was about 300 EGF per cell per min. Conclusion: Low doses of sparsely ionizing radiation can induce shedding of cytokines with the potential to stimulate cell proliferation.