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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

Venn diagram showing overlap patterns of genes which were show to be significantly modulated via microarray in peripheral blood mononuclear cells after various doses of α-particle radiation. Based on an n = 12 human donors.
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Figure 3: Venn diagram showing overlap patterns of genes which were show to be significantly modulated via microarray in peripheral blood mononuclear cells after various doses of α-particle radiation. Based on an n = 12 human donors.

Mentions: Genomic profiling was performed on RNA extracted from isolated PBMCs 24 hr post-exposure. In order to identify biomarkers, statistical stringency was prioritized to mine for reliable genes using a Benjamini Hochberg (BH) false discovery rate (FDR) correction. All differentially expressed genes were filtered on flagged spots and a BH FDR corrected p-value <0.05. A numeric summary of the gene responses at each of the doses is provided in Table 2. Overall, there was a pronounced induction of transcriptional response, with the majority of genes being up-regulated in the presence of the radiation insult. Escalating doses induced an increasing number of transcripts with 30, 69 and 137 genes differentially modified at 0.5, 1.0 and 1.5 Gy respectively. A Venn diagram was constructed to provide a quantitative representation of the similarities and differences in expression profiles at each of the doses (Figure 3). Twenty-nine genes were shown to be differentially expressed at all three doses with expression levels ranging from 2-10 fold. Thirty-nine genes were common between differentially expressed gene sets at both the medium (1.0 Gy) and high (1.5 Gy) dose. The range in expression levels of these 68 genes is summarized as a heat map which delineates the genes by degree of fold change (Figure 4).


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

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

Venn diagram showing overlap patterns of genes which were show to be significantly modulated via microarray in peripheral blood mononuclear cells after various doses of α-particle radiation. Based on an n = 12 human donors.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Venn diagram showing overlap patterns of genes which were show to be significantly modulated via microarray in peripheral blood mononuclear cells after various doses of α-particle radiation. Based on an n = 12 human donors.
Mentions: Genomic profiling was performed on RNA extracted from isolated PBMCs 24 hr post-exposure. In order to identify biomarkers, statistical stringency was prioritized to mine for reliable genes using a Benjamini Hochberg (BH) false discovery rate (FDR) correction. All differentially expressed genes were filtered on flagged spots and a BH FDR corrected p-value <0.05. A numeric summary of the gene responses at each of the doses is provided in Table 2. Overall, there was a pronounced induction of transcriptional response, with the majority of genes being up-regulated in the presence of the radiation insult. Escalating doses induced an increasing number of transcripts with 30, 69 and 137 genes differentially modified at 0.5, 1.0 and 1.5 Gy respectively. A Venn diagram was constructed to provide a quantitative representation of the similarities and differences in expression profiles at each of the doses (Figure 3). Twenty-nine genes were shown to be differentially expressed at all three doses with expression levels ranging from 2-10 fold. Thirty-nine genes were common between differentially expressed gene sets at both the medium (1.0 Gy) and high (1.5 Gy) dose. The range in expression levels of these 68 genes is summarized as a heat map which delineates the genes by degree of fold change (Figure 4).

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