Research Papers:
Radiation therapy induces the DNA damage response in peripheral blood
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Christopher J. Bakkenist1,2,3, R. Kenneth Czambel4, David A. Clump1, Joel S. Greenberger1,5, Jan H. Beumer4,6 and John C. Schmitz4,7
1 Department of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
2 Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
3 Molecular and Cellular Cancer Biology Program, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA, USA
4 Molecular Therapeutics and Drug Discovery Program, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA, USA
5 Lung and Thoracic Malignancies Program, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA, USA
6 Department of Pharmaceutical Sciences, University of Pittsburgh School of Pharmacy, Pittsburgh, PA, USA
7 Division of Hematology Oncology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
Correspondence:
John C. Schmitz, email:
Keywords: DNA damage response, ATM
Received: June 10, 2013 Accepted: June 24, 2013 Published: June 26, 2013
Abstract
Stereotactic body radiation therapy (SBRT) is a radiotherapy modality that delivers highly conformal, ablative doses to a well-defined target. Here, using a semiquantitative multiplexed assay to analyze ATM and H2AX phosphorylation, we show that ATM kinase activity in peripheral blood mononuclear cells is induced following SBRT. This observation of a systemic ATM kinase-dependent DNA damage response in the peripheral blood is unprecedented and promotes the use of ATM serine-1981 phosphorylation as a predictive biomarker for DNA damaging modalities and ATM inhibitors.