Gene Expression Profiles in Mouse Liver after Long-Term Low-Dose-Rate Irradiation with Gamma Rays

Uehara, Yoshio; Ito, Yasuko; Taki, Keiko; Nenoi, Mitsuru; Ichinohe, Kazuaki; Nakamura, Shingo; Tanaka, Satoshi; Oghiso, Yoichi; Tanaka, Kimio; Matsumoto, Tsuneya; Paunesku, Tatjana; Woloschak, Gayle E.; Ono, Tetsuya

doi:10.1667/rr2195.1

Cited by 35 publications

(20 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although some LDR gene profiling studies have been reported, these have been aimed towards the effects of occupational or environmental exposures, and have used mice exposed to much lower dose rates and/or total doses not of concern for radiological triage (36–39). Studies of humans occupationally exposed over many years to low total doses (40, 41) have also been published.…”

Section: Discussionmentioning

confidence: 99%

Radiation Dose-Rate Effects on Gene Expression in a Mouse Biodosimetry Model

et al. 2015

View full text Add to dashboard Cite

In the event of a nuclear accident or radiological terrorist attack, there will be a pressing need for biodosimetry to triage a large, potentially exposed population and to assign individuals to appropriate treatment. Exposures from fallout are likely, resulting in protracted dose delivery that would, in turn, impact the extent of injury. Biodosimetry approaches that can distinguish such low-dose-rate (LDR) exposures from acute exposures have not yet been developed. In this study, we used the C57BL/6 mouse model in an initial investigation of the impact of low-dose-rate delivery on the transcriptomic response in blood. While a large number of the same genes responded to LDR and acute radiation exposures, for many genes the magnitude of response was lower after LDR exposures. Some genes, however, were differentially expressed (P < 0.001, false discovery rate < 5%) in mice exposed to LDR compared with mice exposed to acute radiation. We identified a set of 164 genes that correctly classified 97% of the samples in this experiment as exposed to acute or LDR radiation using a support vector machine algorithm. Gene expression is a promising approach to radiation biodosimetry, enhanced greatly by this first demonstration of its potential for distinguishing between acute and LDR exposures. Further development of this aspect of radiation biodosimetry, either as part of a complete gene expression biodosimetry test or as an adjunct to other methods, could provide vital triage information in a mass radiological casualty event.

show abstract

Section: Discussionmentioning

confidence: 99%

Radiation Dose-Rate Effects on Gene Expression in a Mouse Biodosimetry Model

et al. 2015

View full text Add to dashboard Cite

show abstract

“…exposed mice to a range of low doses of external beam 57 Co at a dose rate of approximately 0.003 mGy/min (35), or to protons at approximately 0.02 mGy/min (36), and reported significant changes in the expression of several genes immediately after exposure. In another study, exposure to a range of low-dose rates at or below 0.013 mGy/min for more than 400 days resulted in small changes in a small number of genes (14). Another study exposed mice for 1–40 days to external gamma rays delivered at a constant 2.8 mGy/min (37) and reported a consistent overexpression of some p53 regulated genes.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2014

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

“…However, although in these studies, the doses and the dose rates met the criteria of the United Nations Scientific Committee on the Effects of Atomic Radiation (13) for being either LD (≤200 mGy) or LDR (≤6 mGy/h), the effects of the LD and LDR irradiation on gene expression were not elucidated. In line with these studies, Taki et al (14) discovered that heat-shock proteins and DNA repair genes were expressed in LDR-irradiated (0.032-12 μGy/min; final dose, 0.02-8 Gy) C57BL/6J mice, whereas Uehara et al (15) found that obesity-and tumorigenesis-related genes were downregulated in the livers of LDR-irradiated (0.042-20 mGy/d; final dose, 0.02-8 Gy) C57BL/6J mice.…”

Section: Introductionmentioning

confidence: 92%