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Radioprotective effects of ATP in human blood ex vivo
Authors:Els LR Swennen  Pieter C Dagnelie  Aalt Bast
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
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.
Keywords:ATP  Radioprotection  Blood  DNA damage  Inflammation  TNF-α  IL-10  Oxidative stress  Irradiation
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