Radioprotective effects of ATP in human blood ex vivo |
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Authors: | Els LR Swennen Pieter C Dagnelie Aalt Bast |
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Institution: | a Department of Epidemiology, NUTRIM Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands b Department of Pharmacology and Toxicology, NUTRIM Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands c Department of Radiation Oncology, Maastricht Radiation oncology (Maastro) Lab, GROW, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands |
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Abstract: | Damage to healthy tissue is a major limitation of radiotherapy treatment of cancer patients, leading to several side effects and complications. Radiation-induced release of pro-inflammatory cytokines is thought to be partially responsible for the radiation-associated complications. The aim of the present study was to investigate the protective effects of extracellular ATP on markers of oxidative stress, radiation-induced inflammation and DNA damage in irradiated blood ex vivo. ATP inhibited radiation-induced TNF-α release and increased IL-10 release. The inhibitory effect of ATP on TNF- α release was completely reversed by adenosine 5′-O-thiomonophosphate, indicating a P2Y11 mediated effect. Furthermore, ATP attenuated radiation-induced DNA damage immediate, 3 and 6 h after irradiation. Our study indicates that ATP administration alleviates radiation-toxicity to blood cells, mainly by inhibiting radiation-induced inflammation and DNA damage. |
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Keywords: | ATP Radioprotection Blood DNA damage Inflammation TNF-α IL-10 Oxidative stress Irradiation |
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