Accurate Gene Expression-Based Biodosimetry Using a Minimal Set of Human Gene Transcripts

Tucker, James D.; Joiner, Michael C.; Thomas, Robert A.; Grever, William E.; Bakhmutsky, Marina V.; Chinkhota, Chantelle N.; Smolinski, J.; Divine, George; Auner, Gregory W.

doi:10.1016/j.ijrobp.2013.11.248

Cited by 43 publications

(44 citation statements)

References 29 publications

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“…Collectively, a higher accuracy was observed for the FDXR gene compared to RAD51 gene. Whole genome microarray analysis predicted the dose of validation samples with an accuracy higher than 90% (Tucker JD, et al 2014). These data suggest that GE analysis of the FDXR for quantitative dose assessment in TBE is more reliable than the expression analysis of the RAD51 gene.…”

Section: Discussionmentioning

confidence: 83%

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Gene Expression Biodosimetry: Quantitative Assessment of Radiation Dose with Total Body Exposure of Rats

Saberi

Khodamoradi²,

Birgani³

et al. 2016

Asian Pacific Journal of Cancer Prevention

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Background: Accurate dose assessment and correct identification of irradiated from non-irradiated people are goals of biological dosimetry in radiation accidents. Objectives: Changes in the FDXR and the RAD51 gene expression (GE) levels were here analyzed in response to total body exposure (TBE) to a 6 MV x-ray beam in rats. We determined the accuracy for absolute quantification of GE to predict the dose at 24 hours. Materials and Methods: For this in vivo experimental study, using simple randomized sampling, peripheral blood samples were collected from a total of 20 Wistar rats at 24 hours following exposure of total body to 6 MV X-ray beam energy with doses (0.2, 0.5, 2 and 4 Gy) for TBE in Linac Varian 2100C/D (Varian, USA) in Golestan Hospital, in Ahvaz, Iran. Also, 9 rats was irradiated with a 6MV X-ray beam at doses of 1, 2, 3 Gy in 6MV energy as a validation group. A sham group was also included. After RNA extraction and DNA synthesis, GE changes were measured by the QRT-PCR technique and an absolute quantification strategy by taqman methodology in peripheral blood from rats. ROC analysis was used to distinguish irradiated from non-irradiated samples (qualitative dose assessment) at a dose of 2 Gy. Results: The best fits for mean of responses were polynomial equations with a R2 of 0.98 and 0.90 (for FDXR and RAD51 dose response curves, respectively). Dose response of the FDXR gene produced a better mean dose estimation of irradiated "validation" samples compared to the RAD51 gene at doses of 1, 2 and 3 Gy. FDXR gene expression separated the irradiated rats from controls with a sensitivity, specificity and accuracy of 87.5%, 83.5% and 81.3%, respectively, 24 hours after dose of 2 Gy. These values were significantly (p<0.05) higher than the 75%, 75% and 75%, respectively, obtained using gene expression of RAD51 analysis at a dose of 2 Gy. Conclusions: Collectively, these data suggest that absolute quantification by gel purified quantitative RT-PCR can be used to measure the mRNA copies for GE biodosimetry studies at comparable accuracy to similar methods. In the case of TBE with 6MV energy, FDXR gene expression analysis is more precise than that with RAD51 for quantitative and qualitative dose assessment.

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Section: Discussionmentioning

confidence: 83%

“…There are two approaches for analyzing the GE that have been used extensively for biodosimetry: microarray and quantitative RT-PCR (Tucker et al 2014). The measurement of changes in the GE by quantitative RT-PCR is more sensitive than that using the microarray method (Kabacik et al 2011).…”

Section: Introductionmentioning

confidence: 99%

Gene Expression Biodosimetry: Quantitative Assessment of Radiation Dose with Total Body Exposure of Rats

Saberi

Khodamoradi²,

Birgani³

et al. 2016

Asian Pacific Journal of Cancer Prevention

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“…Frequency of occurrence of cells with dumbbell-shaped nuclei depends on the dose of irradiation and this correlation is described by a linearquadratic function with the following equation: y = 0.003+0.014x +0.005x 2 [31]. We would like to emphasize that the simplest biomarkers (nuclei abnormalities) we suggest for radiation exposure detection in vivo is not an alternative to classical radiation biomarkers in vitro [17], as well as to other modern approaches [2][3][4][5][44][45][46]. Detection of chromosomal aberrations (dicentrics) and the cytochalasine B micronucleus and "Cytome" methods are reliable bioindication and biodosimetry methods.…”

Section: Dumbbell-shaped Nucleimentioning

confidence: 99%

“…The field of activity of biodosimetry has significantly expanded with the methods of genomics [1,2], proteomics [3,4], metabolomics [5] and transcriptomics [6]. At the same time, methods of cytogenetics that require the cultivation of lymphocytes in vitro or the use of special equipment still remain the classical methods [7][8][9][10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Nuclear Abnormalities of Lymphocytes as the Simplest Markers for Bioindication Test in Case of Mass Casualty Events Involving Radiation Exposure

Kravtsov¹,

Livanova²,

Starkova³

2017

Emerg Med

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Radiation exposure leads to a large number of victims who seek medical help in the first hours. To provide medical care, it is necessary to correctly establish the fact and dose of radiation by bioindication and biodosimetry methods. Lymphocytes containing nuclear anomalies are easily detected cells of peripheral blood and are suitable as objects of bioindication in the case of radioactive exposure to a large number of people. Among these anomalies we distinguish micronuclei, "tailed" nuclei, nucleoplasmatic bridges, dumbbell-shaped nuclei, etc. This review observes the main types of these nuclear anomalies of lymphocytes in the light of their common origin from dicentric chromosomes. We recommend using these alterations in peripheral blood lymphocytes nuclei as the simplest biomarkers in the framework of bioindication tests when it is necessary to work with a large number of victims.

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“…New radiation-responsive biomarkers can be found and corresponding assays developed due to advances in proteomics (22) and genomics (23) . For these assays, the same approach of using the combination of tubes organised in standardised racks for blood collection and multiwell plates for screening can be used.…”

Section: Future Developmentsmentioning

confidence: 99%

Next generation platforms for high-throughput biodosimetry

Repin

Turner

Garty

et al. 2014

Radiation Protection Dosimetry

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Accurate Gene Expression-Based Biodosimetry Using a Minimal Set of Human Gene Transcripts

Cited by 43 publications

References 29 publications

Gene Expression Biodosimetry: Quantitative Assessment of Radiation Dose with Total Body Exposure of Rats

Gene Expression Biodosimetry: Quantitative Assessment of Radiation Dose with Total Body Exposure of Rats

Nuclear Abnormalities of Lymphocytes as the Simplest Markers for Bioindication Test in Case of Mass Casualty Events Involving Radiation Exposure

Next generation platforms for high-throughput biodosimetry

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