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首页> 外文期刊>Toxicology Letters: An International Journal Providing a Forum for Original and Pertinent Contributions in Toxicology Research >Proteome changes in rat serum after a chronic ingestion of enriched uranium: Toward a biological signature of internal contamination and radiological effect
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Proteome changes in rat serum after a chronic ingestion of enriched uranium: Toward a biological signature of internal contamination and radiological effect

机译：富含铀慢性摄入后大鼠血清的蛋白质组变化：朝着内部污染和放射效应的生物签名

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The civilian and military use of uranium results in an increased risk of human exposure. The toxicity of uranium results from both its chemical and radiological properties that vary with isotopic composition. Validated biomarkers of health effects associated with exposure to uranium are neither sensitive nor specific to uranium radiotoxicity and/or radiological effect. This study aimed at investigating if serum proteins could be useful as biomarkers of both uranium exposure and radiological effect. Male Sprague-Dawley rats were chronically exposed through drinking water to low levels (40 mg/L, corresponding to 1 mg of uranium per animal per day) of either 4% U-235-enriched uranium (EU) or 12% EU during 6 weeks. A proteomics approach based on two-dimensional electrophoresis (2D-DIGE) and mass spectrometry (MS) was used to establish protein expression profiles that could be relevant for discriminating between groups, and to identify some differentially expressed proteins following uranium ingestion. It demonstrated that the expressions of 174 protein spots over 1045 quantified spots were altered after uranium exposure (p < 0.05). Using both inferential and non-supervised multivariate statistics, we show sets of spots features that lead to a clear discrimination between controls and EU exposed groups on the one hand (21 spots), and between 4% EU and 12% EU on the other hand (7 spots), showing that investigation of the serum proteome may possibly be of relevance to address both uranium contamination and radiological effect. Finally, using bioinformatics tools, pathway analyses of differentially expressed MS-identified proteins find that acute phase, inflammatory and immune responses as well as oxidative stress are likely involved in the response to contamination, suggesting a physiological perturbation, but that does not necessarily lead to a toxic effect. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
机译：平民和军事利用铀导致人体暴露风险增加。铀的毒性由其化学和放射性特性产生的铀，其含有同位素组合物。验证了与铀接触相关的健康效果的生物标志物既不敏感，也不是铀辐射毒性和/或放射学效应。该研究旨在调查血清蛋白是否可用作铀曝光和放射效应的生物标志物。雄性Sprague-Dawley大鼠通过饮用水慢慢地暴露于低水平（40mg / L，对应于每只动物每只动物的1mg铀），在6期间4％U-235富含铀（EU）或12％EU周。使用基于二维电泳（2D-Dige）和质谱（MS）的蛋白质组学方法来建立蛋白质表达谱，该蛋白表达谱可以与组之间的区分相关，并鉴定铀摄入后一些差异表达的蛋白质。它证明，在铀曝光后改变了174个蛋白质斑点超过1045个定量斑点的表达（P <0.05）。使用介绍和非监督多元统计数据，我们展示了一组控制和欧盟暴露在一方面（21斑点）的明显歧视的斑点特征，另一方面，在4％欧盟和12％欧盟之间进行了明显的歧视（7个斑点），表明血清蛋白质组的研究可能与解决铀污染和放射效应的相关性有关。最后，使用生物信息学工具，差异表达的MS鉴定的蛋白质的途径分析发现急性期，炎症和免疫应答以及氧化应激可能参与污染的反应，表明生理扰动，但这并不一定导致毒性效果。 （c）2016 Elsevier Ireland Ltd.保留所有权利。

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