A model of cytokine shedding induced by low doses of gamma radiation

J. H. Miller, F. Zheng, S. Jin, L. K. Opresko, H. S. Wiley, H. Resat

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

A model for sustained shedding of epidermal growth factor (EGF) in response to low doses of gamma radiation was developed based on a time delay in the feedback from mitogen-activated protein kinase (MAPK) activation to metalloprotease activity in an autocrine signaling process. We determined the kinetic parameters of our model using the data available for MAPK activation by γ irradiation in the 1-2-Gy dose range and then showed that predictions of the model were consistent with experimental results for the kinetics of EGF shedding into the growth medium after exposure of human mammary epithelial cells to 1-5 cGy of γ radiation in the presence of antibodies that block ligand binding to EGF receptors. The model allowed us to estimate the rate of radiation-induced cytokine release per cell from measurements of EGF concentration in the growth medium and to assess the effectiveness of EGF shedding and subsequent diffusion through the medium as a mechanism for signal transmission between hit cells and bystanders.

Original languageEnglish
Pages (from-to)337-342
Number of pages6
JournalRadiation Research
Volume163
Issue number3
DOIs
StatePublished - Mar 2005

ASJC Scopus subject areas

  • Biophysics
  • Radiation
  • Radiology Nuclear Medicine and imaging

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