Research Papers:

Radiation therapy generates platelet-activating factor agonists

Ravi P. Sahu _, Kathleen A. Harrison, Jonathan Weyerbacher, Robert C. Murphy, Raymond L. Konger, Joy Elizabeth Garrett, Helen Jan Chin-Sinex, Michael Edward Johnston II, Joseph R. Dynlacht, Marc Mendonca, Kevin McMullen, Gengxin Li, Dan F. Spandau and Jeffrey B. Travers

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Oncotarget. 2016; 7:20788-20800. https://doi.org/10.18632/oncotarget.7878

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Ravi P. Sahu1, Kathleen A. Harrison2, Jonathan Weyerbacher3, Robert C. Murphy2, Raymond L. Konger4, Joy Elizabeth Garrett5, Helen Jan Chin-Sinex5, Michael Edward Johnston II3, Joseph R. Dynlacht5, Marc Mendonca5, Kevin McMullen5, Gengxin Li6, Dan F. Spandau3, Jeffrey B. Travers1,3,7

1Department of Pharmacology and Toxicology, Boonshoft School of Medicine at Wright State University, Dayton, OH, USA

2Department of Pharmacology, University of Colorado Health Sciences Center, Aurora, CO, USA

3Department of Dermatology, Indiana University School of Medicine, Indianapolis, IN, USA

4Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA

5Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, IN, USA

6Department of Biostatistics, Wright State University, Dayton, OH, USA

7The Dayton V.A. Medical Center, Dayton, OH, USA

Correspondence to:

Ravi P. Sahu, e-mail: [email protected]

Keywords: radiation therapy, oxidized glycerophosphocholines, platelet-activating factor, cyclooxygenase type 2 enzyme, antioxidants

Received: November 30, 2015    Accepted: February 06, 2016    Published: March 03, 2016


Pro-oxidative stressors can suppress host immunity due to their ability to generate oxidized lipid agonists of the platelet-activating factor-receptor (PAF-R). As radiation therapy also induces reactive oxygen species, the present studies were designed to define whether ionizing radiation could generate PAF-R agonists and if these lipids could subvert host immunity. We demonstrate that radiation exposure of multiple tumor cell lines in-vitro, tumors in-vivo, and human subjects undergoing radiation therapy for skin tumors all generate PAF-R agonists. Structural characterization of radiation-induced PAF-R agonistic activity revealed PAF and multiple oxidized glycerophosphocholines that are produced non-enzymatically. In a murine melanoma tumor model, irradiation of one tumor augmented the growth of the other (non-treated) tumor in a PAF-R-dependent process blocked by a cyclooxygenase-2 inhibitor. These results indicate a novel pathway by which PAF-R agonists produced as a byproduct of radiation therapy could result in tumor treatment failure, and offer important insights into potential therapeutic strategies that could improve the overall antitumor effectiveness of radiation therapy regimens.

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