Proteome changes in rat serum after a chronic ingestion of enriched uranium: Toward a biological signature of internal contamination and radiological effect.
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 (40mg/L, corresponding to 1mg of uranium per animal per day) of either 4% (235)U-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.
Institut de Radioprotection et de Sûreté Nucléaire (IRSN), PRP-HOM, SRBE, LRTOX, Pierrelatte, France.
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Petitot
Institut de Radioprotection et de Sûreté Nucléaire (IRSN), PRP-HOM, SRBE, LRTOX, Pierrelatte, France.
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Frelon
Institut National de la Recherche Agronomique (INRA), PFEM, Composante Protéomique, UR370, Saint-Genès-Champanelle, France.
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Chambon
Institut de Radioprotection et de Sûreté Nucléaire (IRSN), PRP-HOM, SRBE, LRTOX, Pierrelatte, France.
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Paquet
Institut de Radioprotection et de Sûreté Nucléaire (IRSN), PRP-HOM, SRBE, L3R, Fontenay-aux-Roses, France. Electronic address: olivier.guipaud@irsn.fr.
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Guipaud
D000209:Acute-Phase Proteins / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins / Q000378:metabolism*; D016002:Discriminant Analysis; D004326:Drinking; D018836:Inflammation Mediators / Q000097:blood; D008297:Male; D015999:Multivariate Analysis; D018384:Oxidative Stress / Q000528:radiation effects; D025341:Principal Component Analysis; D060066:Protein Interaction Maps; D020543:Proteome; D040901:Proteomics / Q000379:methods; D011832:Radiation Injuries / Q000097:blood* / Q000175:diagnosis; D017207:Rats, Sprague-Dawley; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D057825:Two-Dimensional Difference Gel Electrophoresis; D014501:Uranium / Q000633:toxicity*; D014502:Uranyl Nitrate / Q000633:toxicity*; D014875:Water Pollutants, Radioactive / Q000633:toxicity*
D000209:Acute-Phase Proteins; D015415:Biomarkers; D001798:Blood Proteins; D018836:Inflammation Mediators; D020543:Proteome; D014875:Water Pollutants, Radioactive; D014502:Uranyl Nitrate; D014501:Uranium
Acute phase proteins; Chronic ingestion; Proteomics; Serum; Uranium