title: Effect of 90Sr internal emitter on gene expression in mouse blood.
abstract: 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.
authors.affiliation: Center for Radiological Research, Columbia University Medical Center, VC11-215, 630 West 168th Street, New York, NY, 10032, USA. sg2423@cumc.columbia.edu.
authors.forename: Shanaz A
authors.initials: SA
authors.lastname: Ghandhi
authors.affiliation: Lovelace Respiratory Research Institute, Albuquerque, NM, 87108, USA. wweber@lrri.org.
authors.forename: Waylon
authors.initials: W
authors.lastname: Weber
authors.affiliation: Lovelace Respiratory Research Institute, Albuquerque, NM, 87108, USA. dmelo@lrri.org.
authors.forename: Dunstana
authors.initials: D
authors.lastname: Melo
authors.affiliation: Lovelace Respiratory Research Institute, Albuquerque, NM, 87108, USA. mdoyle@lrri.org.
authors.forename: Melanie
authors.initials: M
authors.lastname: Doyle-Eisele
authors.affiliation: Center for Radiological Research, Columbia University Medical Center, VC11-215, 630 West 168th Street, New York, NY, 10032, USA. mc3102@columbia.edu.
authors.forename: Mashkura
authors.initials: M
authors.lastname: Chowdhury
authors.affiliation: Lovelace Respiratory Research Institute, Albuquerque, NM, 87108, USA. rayguilmette7530@gmail.com.
authors.forename: Raymond
authors.initials: R
authors.lastname: Guilmette
authors.affiliation: Center for Radiological Research, Columbia University Medical Center, VC11-215, 630 West 168th Street, New York, NY, 10032, USA. saa2108@cumc.columbia.edu.
authors.forename: Sally A
authors.initials: SA
authors.lastname: Amundson
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001402:B-Lymphocytes / Q000528:radiation effects; D015870:Gene Expression / Q000235:genetics / Q000528:radiation effects*; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000235:genetics / Q000528:radiation effects*; D050356:Lipid Metabolism / Q000235:genetics / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D018788:Radioactive Hazard Release; D013325:Strontium Isotopes / Q000009:adverse effects*; D013601:T-Lymphocytes / Q000528:radiation effects
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger; D013325:Strontium Isotopes