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Effect of 90Sr internal emitter on gene expression in mouse blood
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Effect of 90Sr internal emitter on gene expression in mouse blood
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Journal Article
Effect of 90Sr internal emitter on gene expression in mouse blood
2015
Overview
Background
The radioactive isotope Strontium-90 (
90
Sr) 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
90
Sr, using an easily attainable and standard biodosimetry sample fluid, we analyzed the global transcriptomic response of blood cells in an
in vivo
model system.
Results
We 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
90
Sr 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.
Conclusions
Our study is the first to report the transcriptomic response of blood cells to the internal emitter
90
Sr in mouse and a possible role for microRNA in gene regulation after
90
Sr 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.
Publisher
BioMed Central,BioMed Central Ltd,Springer Nature B.V
Subject
/ Animals
/ B-Lymphocytes - radiation effects
/ Biomedical and Life Sciences
/ Gene Expression - radiation effects
/ Gene Expression Profiling - methods
/ Gene Expression Regulation - genetics
/ Gene Expression Regulation - radiation effects
/ Lipid Metabolism - radiation effects
/ Mice
/ Microbial Genetics and Genomics
/ Strontium Isotopes - adverse effects
/ T cells
