Sahu, Ravi P.Harrison, Kathleen A.Weyerbacher, JonathanMurphy, Robert C.Konger, Raymond L.Garrett, Joy ElizabethChin-Sinex, Helen JanJohnston II., Michael EdwardDynlacht, Joseph R.Mendonca, MarcMcMullen, KevinLi, GengxinSpandau, Dan F.Travers, Jeffrey B.2017-05-222017-05-222016-04-12Sahu, R. P., Harrison, K. A., Weyerbacher, J., Murphy, R. C., Konger, R. L., Garrett, J. E., … Travers, J. B. (2016). Radiation therapy generates platelet-activating factor agonists. Oncotarget, 7(15), 20788–20800. http://doi.org/10.18632/oncotarget.7878https://hdl.handle.net/1805/12676Pro-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.en-USAttribution-NonCommercial-NoDerivs 3.0 United StatesRadiation therapyOxidized glycerophosphocholinesPlatelet-activating factorCyclooxygenase type 2 enzymeAntioxidantsArticle