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Identification of gene-based responses in human blood cells exposed to alpha particle radiation.

Chauhan V, Howland M, Wilkins R - BMC Med Genomics (2014)

Bottom Line: Microarray technology was employed to identify transcripts that were differentially expressed relative to unirradiated cells 24 hours post-exposure.Twenty-nine genes were common to all doses with expression levels ranging from 2-10 fold relative to control treatment group.This 29 gene panel was responsive in the α-particle exposed WBCs and was shown to exhibit differential fold-changes compared to X-irradiated cells, though no α-particle specific transcripts were identified.

View Article: PubMed Central - HTML - PubMed

Affiliation: Consumer and Clinical Radiation Protection Bureau, Healthy Environment and Consumer Safety Branch, Health Canada, 775 Brookfield Road, PL 6303B, Ottawa, ON K1A 1C1, Canada. Vinita.chauhan@hc-sc.gc.ca.

ABSTRACT

Background: The threat of a terrorist-precipitated nuclear event places humans at danger for radiological exposures. Isotopes which emit alpha (α)-particle radiation pose the highest risk. Currently, gene expression signatures are being developed for radiation biodosimetry and triage with respect to ionizing photon radiation. This study was designed to determine if similar gene expression profiles are obtained after exposures involving α-particles.

Methods: Peripheral blood mononuclear cells (PBMCs) were used to identify sensitive and robust gene-based biomarkers of α-particle radiation exposure. Cells were isolated from healthy individuals and were irradiated at doses ranging from 0-1.5 Gy. Microarray technology was employed to identify transcripts that were differentially expressed relative to unirradiated cells 24 hours post-exposure. Statistical analysis identified modulated genes at each of the individual doses.

Results: Twenty-nine genes were common to all doses with expression levels ranging from 2-10 fold relative to control treatment group. This subset of genes was further assessed in independent complete white blood cell (WBC) populations exposed to either α-particles or X-rays using quantitative real-time PCR. This 29 gene panel was responsive in the α-particle exposed WBCs and was shown to exhibit differential fold-changes compared to X-irradiated cells, though no α-particle specific transcripts were identified.

Conclusion: Current gene panels for photon radiation may also be applicable for use in α-particle radiation biodosimetry.

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Related in: MedlinePlus

Schematic representation of the experimental process, assays and endpoints (those yielding data are shaded) for the A) peripheral blood mononuclear cell and B) the white blood cell populations.
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Figure 1: Schematic representation of the experimental process, assays and endpoints (those yielding data are shaded) for the A) peripheral blood mononuclear cell and B) the white blood cell populations.

Mentions: All procedures were approved by Health Canada’s Research Ethics Committee and a flow chart delineating the experimental sequence is outlined in Figure 1. Briefly, peripheral blood from healthy, non-smoking volunteers was drawn via periphery venipuncture with informed consent from all subjects into either 5 × 10 ml EDTA (for gene analysis) or 2 × 4 ml lithium heparin (for plasma analysis) vacutainer tubes (Becton Dickinson and Company, Franklin Lakes, NJ). A total of 6 male and 6 female donors participated. Before any further processing, a 100 μl whole blood sample was used for a complete blood count (CBC) via automatic haemocytometer (Beckman Coulter, Mississauga, ON).


Identification of gene-based responses in human blood cells exposed to alpha particle radiation.

Chauhan V, Howland M, Wilkins R - BMC Med Genomics (2014)

Schematic representation of the experimental process, assays and endpoints (those yielding data are shaded) for the A) peripheral blood mononuclear cell and B) the white blood cell populations.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4128605&req=5

Figure 1: Schematic representation of the experimental process, assays and endpoints (those yielding data are shaded) for the A) peripheral blood mononuclear cell and B) the white blood cell populations.
Mentions: All procedures were approved by Health Canada’s Research Ethics Committee and a flow chart delineating the experimental sequence is outlined in Figure 1. Briefly, peripheral blood from healthy, non-smoking volunteers was drawn via periphery venipuncture with informed consent from all subjects into either 5 × 10 ml EDTA (for gene analysis) or 2 × 4 ml lithium heparin (for plasma analysis) vacutainer tubes (Becton Dickinson and Company, Franklin Lakes, NJ). A total of 6 male and 6 female donors participated. Before any further processing, a 100 μl whole blood sample was used for a complete blood count (CBC) via automatic haemocytometer (Beckman Coulter, Mississauga, ON).

Bottom Line: Microarray technology was employed to identify transcripts that were differentially expressed relative to unirradiated cells 24 hours post-exposure.Twenty-nine genes were common to all doses with expression levels ranging from 2-10 fold relative to control treatment group.This 29 gene panel was responsive in the α-particle exposed WBCs and was shown to exhibit differential fold-changes compared to X-irradiated cells, though no α-particle specific transcripts were identified.

View Article: PubMed Central - HTML - PubMed

Affiliation: Consumer and Clinical Radiation Protection Bureau, Healthy Environment and Consumer Safety Branch, Health Canada, 775 Brookfield Road, PL 6303B, Ottawa, ON K1A 1C1, Canada. Vinita.chauhan@hc-sc.gc.ca.

ABSTRACT

Background: The threat of a terrorist-precipitated nuclear event places humans at danger for radiological exposures. Isotopes which emit alpha (α)-particle radiation pose the highest risk. Currently, gene expression signatures are being developed for radiation biodosimetry and triage with respect to ionizing photon radiation. This study was designed to determine if similar gene expression profiles are obtained after exposures involving α-particles.

Methods: Peripheral blood mononuclear cells (PBMCs) were used to identify sensitive and robust gene-based biomarkers of α-particle radiation exposure. Cells were isolated from healthy individuals and were irradiated at doses ranging from 0-1.5 Gy. Microarray technology was employed to identify transcripts that were differentially expressed relative to unirradiated cells 24 hours post-exposure. Statistical analysis identified modulated genes at each of the individual doses.

Results: Twenty-nine genes were common to all doses with expression levels ranging from 2-10 fold relative to control treatment group. This subset of genes was further assessed in independent complete white blood cell (WBC) populations exposed to either α-particles or X-rays using quantitative real-time PCR. This 29 gene panel was responsive in the α-particle exposed WBCs and was shown to exhibit differential fold-changes compared to X-irradiated cells, though no α-particle specific transcripts were identified.

Conclusion: Current gene panels for photon radiation may also be applicable for use in α-particle radiation biodosimetry.

Show MeSH
Related in: MedlinePlus