Development of Urinary Biomarkers for Internal Exposure by Cesium-137 Using a Metabolomics Approach in Mice

Goudarzi, Maryam; Weber, Waylon; Mak, Tytus D.; Chung, Juijung; Doyle-Eisele, Melanie; Melo, Dunstana R.; Brenner, David J.; Guilmette, Raymond A.; Fornace, Albert J.

doi:10.1667/rr13479.1

Cited by 53 publications

(77 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The ion at m/z of 191.0201 ([M — H] – ) was identified as citrate whose urinary excretion dropped in both HDR- and LDR-exposed mice post-irradiation. This is in accordance with our previous external γ-irradiation study and an internal emitter exposure study where mice were injected with 137 CsCl (Goudarzi et al 2013). Figure 3 also displays ions with varying behavior between HDR and LDR and their levels indicate a dose rate response.…”

Section: Resultssupporting

confidence: 92%

“…The same is true for two carnitine species, tiglylcarnitine and hexanoylcarnitine. Hexanoylcarnitine was determined to show a similar decreasing trend in another LDR study with 137 Cs exposure (Goudarzi et al 2013). Table 5 compares the urinary excretion patterns of several metabolites from this study, which also have been mentioned in other IR studies.…”

Section: Resultsmentioning

confidence: 81%

“…It is important to develop early biomarkers, as LDR exposure to fallout and internal emitters will occur over an extended period of time. We have already shown a clear metabolomic response to an internal emitter (Goudarzi et al 2013). In this study, we focused on establishing a metabolomic profile for HDR exposure and LDR exposure to highlight their subtle dif-ferences, as well as similarities using a wide array of sta-tistical tools.…”

Section: Introductionmentioning

confidence: 88%

See 2 more Smart Citations

The effect of low dose rate on metabolomic response to radiation in mice

Goudarzi

Mak

Chen

et al. 2014

Radiat Environ Biophys

Self Cite

View full text Add to dashboard Cite

Metabolomics has been shown to have utility in assessing responses to exposure by ionizing radiation (IR) in easily accessible biofluids such as urine. Most studies to date from our laboratory and others have employed γ-irradiation at relatively high dose rates (HDR), but many environmental exposure scenarios will probably be at relatively low dose rates (LDR). There are well-documented differences in the biologic responses to LDR compared to HDR, so an important question is to assess LDR effects at the metabolomics level. Our study took advantage of a modern mass spectrometry approach in exploring the effects of dose rate on the urinary excretion levels of metabolites 2 days after IR in mice. A wide variety of statistical tools were employed to further focus on metabolites, which showed responses to LDR IR exposure (0.00309 Gy/min) distinguishable from those of HDR. From a total of 709 detected spectral features, more than 100 were determined to be statistically significant when comparing urine from mice irradiated with 1.1 or 4.45 Gy to that of sham-irradiated mice 2 days post-exposure. The results of this study show that LDR and HDR exposures perturb many of the same pathways such as TCA cycle and fatty acid metabolism, which also have been implicated in our previous IR studies. However, it is important to note that dose rate did affect the levels of particular metabolites. Differences in urinary excretion levels of such metabolites could potentially be used to assess an individual's exposure in a radiobiological event and thus would have utility for both triage and injury assessment.

show abstract

Section: Resultssupporting

confidence: 92%

Section: Resultsmentioning

confidence: 81%

Section: Introductionmentioning

confidence: 88%

See 1 more Smart Citation

The effect of low dose rate on metabolomic response to radiation in mice

Goudarzi

Mak

Chen

et al. 2014

Radiat Environ Biophys

Self Cite

View full text Add to dashboard Cite

show abstract

“…The effects of internal 137 Cs on the mouse urinary metabolome have also recently been reported in a companion study to our gene expression study (45). The effect of 137 Cs administration on metabolism was found to be most pronounced at earlier times, but changes were found to persist through day 30.…”

Section: Discussionsupporting

confidence: 63%

Gene Expression Response of Mice after a Single Dose of 137Cs as an Internal Emitter

et al. 2014

Self Cite

View full text Add to dashboard Cite

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 137CsCl. We extracted RNA from the blood of control or 137CsCl-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 137Cs 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 137CsCl 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 137Cs, 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.

show abstract

“…Similarly to proteomics, metabolomics is also expected to contribute to space biology. A system was recently established to measure a time-dependent metabolomics profile for urine collected from mice injected with 137 Cs (Goudarzi et al, 2014). It might be useful to detect not only the trace of space-radiation exposure but also the perturbations in several amino acid and fatty acid metabolism pathway during stay in space environment.…”

Section: Gene Expression (Cellular Response)mentioning

confidence: 99%