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

BMC Genomics

Research Article

Mashkura Chowdhury¹  Sally A. Amundson¹  Shanaz A. Ghandhi¹  Dunstana Melo²  Waylon Weber²  Melanie Doyle-Eisele²  Raymond Guilmette² 

[1] Center for Radiological Research, Columbia University Medical Center, VC11-215, 630 West 168th Street, 10032, New York, NY, USA;Lovelace Respiratory Research Institute, 87108, Albuquerque, NM, USA;

关键词: Gene expression;    Microarrays;    Strontium-90;    MicroRNA;    Radiation biodosimetry;   

DOI  :  10.1186/s12864-015-1774-z

 received in 2015-01-22, accepted in 2015-07-14,  发布年份 2015

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY   
© Ghandhi et al. 2015