Effect of 90Sr internal emitter on gene expression in mouse blood

Abstract

BackgroundThe radioactive isotope Strontium-90 (90Sr) may be released as a component of fallout from nuclear accidents, or in the event of a radiological incident such as detonation of an improvised nuclear device, and if ingested poses a significant health risk to exposed individuals. In order to better understand the response to 90Sr, using an easily attainable and standard biodosimetry sample fluid, we analyzed the global transcriptomic response of blood cells in an in vivo model system.ResultsWe injected C57BL/6 mice with a solution of 90SrCl2 and followed them over a 30-day period. At days 4, 7, 9, 25 and 30, we collected blood and isolated RNA for microarray analyses. These days corresponded to target doses in a range from 1–5 Gy. We investigated changes in mRNA levels using microarrays, and changes in specific microRNA (miRNA) predicted to be involved in the response using qRT-PCR. We identified 8082 differentially expressed genes in the blood of mice exposed to 90Sr compared with controls. Common biological functions were affected throughout the study, including apoptosis of B and T lymphocytes, and atrophy of lymphoid organs. Cellular functions such as RNA degradation and lipid metabolism were also affected during the study. The broad down regulation of genes observed in our study suggested a potential role for miRNA in gene regulation. We tested candidate miRNAs, mmu-miR-16, mmu-miR-124, mmu-miR-125 and mmu-mir-21; and found that all were induced at the earliest time point, day 4.ConclusionsOur study is the first to report the transcriptomic response of blood cells to the internal emitter 90Sr in mouse and a possible role for microRNA in gene regulation after 90Sr exposure. The most dramatic effect was observed on gene expression related to B-cell development and RNA maintenance. These functions were affected by genes that were down regulated throughout the study, suggesting severely compromised antigen response, which may be a result of the deposition of the radioisotope proximal to the hematopoietic compartment in bone.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-1774-z) contains supplementary material, which is available to authorized users.

Comparison of gene expression response to neutron and x-ray irradiation using mouse blood

“…These genes were downregulated starting at day 1 and reduced expression persisted until the end of the experiments at day 7. Widespread decreased expression of immune function genes has been shown previously in both human blood irradiated ex vivo, as well as in vivo mouse peripheral blood following ionizing radiation exposure or 90 Sr as an internal emitter [22–24]. High-dose radiation (> 1 Gy) has been shown to disrupt immune cell functions, leading to increased cell death of blood cells in mice [25, 26].…”

γ-H2AX Kinetic Profile in Mouse Lymphocytes Exposed to the Internal Emitters Cesium-137 and Strontium-90

“…In a recently published companion study which measured gene expression transcripts in the same peripheral blood mouse samples exposed to 137 Cs, Paul et al, [ 26 ], reported fewer differentially expressed genes compared to the earlier and later time points at the accrued dose of 4.1 Gy (Day 5), suggesting a general transition point at or around this time since the beginning of exposure. Transcriptomic measurements after low-dose 90 Sr exposure [ 29 ] reported that 8082 genes were affected overall, the majority of which were down-regulated with at least 50% overlap between the successive time points, implying that the effect of 90 Sr was significant throughout the study. Functional analyses were largely related to immune responses, activation of apoptosis of B and T cells, changes in spleen growth, and defects in the response to infection.…”

“…Whole body 137 Cs and 85 Sr/ 90 Sr content was measured using the LBERI in vivo photon counting system described previously in more detail in our companion studies [ 26 – 29 ]. Briefly, LBERI utilizes a pair of dual-scintillator [NaI(Tl)-CsI(Tl)] crystal detectors.…”

Quantitative Metabolomic Analysis of Urinary Citrulline and Calcitroic Acid in Mice after Exposure to Various Types of Ionizing Radiation

“…Several in vivo studies have established changes in the plasma levels of citrulline as a reliable indicator for gastrointestinal (GI) injury and citrulline has even been suggested as a promising biomarker of GI toxicity in patients undergoing chemo- and radiation therapy [ 26 ]. We have also observed a slight yet statistically significant increase in the gene expression of NOS1 in the blood of mice internally exposed to the radionuclide 90 Sr [ 15 , 16 ].…”

“…Despite the important role of vitamin D metabolism and evidence that its metabolic intermediates may attenuate cell death induced by ionizing radiation (IR) exposure [ 14 ], there is little information on the IR-induced changes in the various genes, proteins and metabolites pertaining to this pathway. Our recent gene expression study carried out on the blood of mice exposed to 90 Sr and 137 Cs showed lower expression of two Cyp genes, Cyp4f18 and Cyp4v3 while a higher expression of Cyp4v3 was recorded after HDR exposure [ 15 , 16 , 17 ]. In addition, CYP4 proteins have been shown to metabolize vitamin D and are important in defense against chemical and environmental stressors [ 18 ].…”