Swennen Els L R, Dagnelie Pieter C, Van den Beucken Twan, Bast Aalt
Department of Epidemiology, NUTRIM Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands.
Biochem Biophys Res Commun. 2008 Mar 7;367(2):383-7. doi: 10.1016/j.bbrc.2007.12.125. Epub 2007 Dec 28.
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-alpha release and increased IL-10 release. The inhibitory effect of ATP on TNF- alpha release was completely reversed by adenosine 5'-O-thiomonophosphate, indicating a P2Y(11) mediated effect. Furthermore, ATP attenuated radiation-induced DNA damage immediate, 3 and 6h after irradiation. Our study indicates that ATP administration alleviates radiation-toxicity to blood cells, mainly by inhibiting radiation-induced inflammation and DNA damage.
对健康组织的损伤是癌症患者放射治疗的一个主要限制因素，会导致多种副作用和并发症。辐射诱导促炎细胞因子的释放被认为是辐射相关并发症的部分原因。本研究的目的是在体外研究细胞外ATP对辐照血液中氧化应激标志物、辐射诱导的炎症和DNA损伤的保护作用。ATP抑制辐射诱导的肿瘤坏死因子-α（TNF-α）释放并增加白细胞介素-10（IL-10）释放。5'-O-硫代单磷酸腺苷完全逆转了ATP对TNF-α释放的抑制作用，表明这是一种由P2Y(11)介导的效应。此外，ATP在辐照后即刻、3小时和6小时减轻了辐射诱导的DNA损伤。我们的研究表明，给予ATP可减轻对血细胞的辐射毒性，主要是通过抑制辐射诱导的炎症和DNA损伤来实现。
