Radiation therapy induces the DNA damage response in peripheral blood

Christopher J Bakkenist; R Kenneth Czambel; David A Clump; Joel S Greenberger; Jan H Beumer; John C Schmitz

doi:10.18632/oncotarget.1084

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Research Papers:

Radiation therapy induces the DNA damage response in peripheral blood

Christopher J Bakkenist _, R Kenneth Czambel, David A Clump, Joel S Greenberger, Jan H Beumer and John C Schmitz

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Oncotarget. 2013; 4:1143-1148. https://doi.org/10.18632/oncotarget.1084

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Abstract

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.

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Research Papers:

Radiation therapy induces the DNA damage response in peripheral blood

Abstract