Nanosensor dosimetry of mouse blood proteins after exposure to ionizing radiation.

Department of Materials Science and Engineering, Stanford University, Stanford, California 94305.
Scientific Reports (Impact Factor: 5.08). 07/2013; 3:2234. DOI: 10.1038/srep02234
Source: PubMed

ABSTRACT Giant magnetoresistive (GMR) nanosensors provide a novel approach for measuring protein concentrations in blood for medical diagnosis. Using an in vivo mouse radiation model, we developed protocols for measuring Flt3 ligand (Flt3lg) and serum amyloid A1 (Saa1) in small amounts of blood collected during the first week after X-ray exposures of sham, 0.1, 1, 2, 3, or 6 Gy. Flt3lg concentrations showed excellent dose discrimination at ≥ 1 Gy in the time window of 1 to 7 days after exposure except 1 Gy at day 7. Saa1 dose response was limited to the first two days after exposure. A multiplex assay with both proteins showed improved dose classification accuracy. Our magneto-nanosensor assay demonstrates the dose and time responses, low-dose sensitivity, small volume requirements, and rapid speed that have important advantages in radiation triage biodosimetry.

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    ABSTRACT: Cesium-137 is a radionuclide of concern in fallout from reactor accidents or nuclear detonations. When ingested or inhaled, it can expose the entire body for an extended period of time, potentially contributing to serious health consequences ranging from acute radiation syndrome to increased cancer risks. To identify changes in gene expression that may be informative for detecting such exposure, and to begin examining the molecular responses involved, we have profiled global gene expression in blood of male C57BL/6 mice injected with (137)CsCl. We extracted RNA from the blood of control or (137)CsCl-injected mice at 2, 3, 5, 20 or 30 days after exposure. Gene expression was measured using Agilent Whole Mouse Genome Microarrays, and the data was analyzed using BRB-ArrayTools. Between 466-6,213 genes were differentially expressed, depending on the time after (137)Cs administration. At early times (2-3 days), the majority of responsive genes were expressed above control levels, while at later times (20-30 days) most responding genes were expressed below control levels. Numerous genes were overexpressed by day 2 or 3, and then underexpressed by day 20 or 30, including many Tp53-regulated genes. The same pattern was seen among significantly enriched gene ontology categories, including those related to nucleotide binding, protein localization and modification, actin and the cytoskeleton, and in the integrin signaling canonical pathway. We compared the expression of several genes three days after (137)CsCl injection and three days after an acute external gamma-ray exposure, and found that the internal exposure appeared to produce a more sustained response. Many common radiation-responsive genes are altered by internally administered (137)Cs, but the gene expression pattern resulting from continued irradiation at a decreasing dose rate is extremely complex, and appears to involve a late reversal of much of the initial response. © 2014 by Radiation Research Society.
    Radiation Research 08/2014; 182(4). DOI:10.1667/RR13466.1 · 2.45 Impact Factor


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Jun 2, 2014