Differential Gene Expression in Primary Human Skin Keratinocytes and Fibroblasts in Response to Ionizing Radiation

Warters, Raymond L.; Packard, Ann T.; Kramer, Gwen; Gaffney, David K.; Moos, Philip J.

doi:10.1667/rr1677.1

Cited by 47 publications

(40 citation statements)

References 56 publications

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“…Strongly upregulated expression of the CDKN1A gene shown in this study slightly different from previous findings that showed only a several- or 10-fold increase in CDKN1A gene expression after radiation (from 4-fold to 10- or 50-fold or greater increase) [11,16,35–38]. It is supposed that the difference of testing mode, primary design of CDKN1A gene composition and application of the primaries might be responsible for the diversity of the results.…”

Section: Discussioncontrasting

confidence: 99%

Radiation dose effect of DNA repair-related gene expression in mouse white blood cells

Wang

Chen

et al. 2011

Med Sci Monit

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SummaryBackgroundThe aim of this study was to screen molecular biomarkers for biodosimetry from DNA repair-related gene expression profiles.Material/MethodsMice were subjected to whole-body exposure with 60Co γ rays with a dose range of 0–8 Gy at a dose rate of 0.80 Gy/min. RNA was extracted from the peripheral blood of irradiated mice at 4, 8, 12, 24 and 48hrs post-irradiation. The mRNA transcriptional changes of 11 genes related to DNA damage and repair were detected using real-time quantitative polymerase chain reaction (RT-PCR).ResultsOf the 11 genes examined, CDKN1A (cyclin-dependent kinase inhibitor 1A or p21, Cip1) and ATM (ataxia telangiectasia mutated) expression levels were found to be heavily up- and down-regulated, respectively, with exposure dose increasing at different post-irradiation times. RAD50 (RAD50 homolog), PLK3 (polo-like kinase 3), GADD45A (growth arrest and DNA damage-inducible, alpha), DDB2 (damage-specific DNA-binding protein 2), BBC3 (BCL2-binding component 3) and IER5 (immediate early response 5) gene expression levels were found to undergo significant oscillating changes over a broad dose range of 2–8 Gy at post-exposure time points observed. Three of the genes were found not to change within the observed exposure dose and post-radiation time ranges.ConclusionsThe results of this study add to the biodosimetry with biomarker data pool and will be helpful for constructing appropriate gene expression biomarker systems to evaluate radiation exposure doses.

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Section: Discussioncontrasting

confidence: 99%

Radiation dose effect of DNA repair-related gene expression in mouse white blood cells

Wang

Chen

et al. 2011

Med Sci Monit

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“…The predominant p53-elicited transcriptional response of hESC to IR exposures at early timepoint such as 2 hr resembles that observed in adult differentiated human somatic cells [11]. However, induction of p53 in pluripotent cells was shown to have some stem cell-specific consequences.…”

Section: Resultsmentioning

confidence: 95%

“…With the development of newer, high-throughput technology it became possible to interrogate the expression of thousands of genes simultaneously following specific treatment conditions [5], including genotoxic agent exposures [6]. These functional genomics experiments vastly extended our knowledge how human cells of different origins respond to IR [7–11]. DNA microarray profiling enabled identification of novel radiation-responsive signaling pathways, further advancing our understanding of IR effects on humans [12].…”

Section: Introductionmentioning

confidence: 99%

Dynamics of the transcriptome response of cultured human embryonic stem cells to ionizing radiation exposure

Sokolov

Panyutin

et al. 2011

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

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One of the key consequences of exposure of human cells to genotoxic agents is the activation of DNA damage responses (DDR). While the mechanisms underpinning DDR in fully differentiated somatic human cells have been studied extensively, molecular signaling events and pathways involved in DDR in pluripotent human embryonic stem cells (hESC) remain largely unexplored. We studied changes in the human genome-wide transcriptome of H9 hESC line following exposures to 1 Gy of gamma-radiation at 2 hrs and 16 hrs post-irradiation. Quantitative real-time PCR was performed to verify the expression data for a subset of genes. In parallel, the cell growth, DDR kinetics, and expression of pluripotency markers in irradiated hESC were monitored. The changes in gene expression in hESC after exposure to ionizing radiation (IR) are substantially different from those observed in somatic human cell lines. Gene expression patterns at 2 hr post-IR showed almost an exclusively p53-dependent, predominantly pro-apoptotic, signature with a total of only 30 up-regulated genes. In contrast, the gene expression patterns at 16 hr post-IR showed 354 differentially expressed genes, mostly involved in pro-survival pathways, such as increased expression of metallothioneins, ubiquitin cycle, and general metabolism signaling. Cell growth data paralleled trends in gene expression changes. DDR in hESC followed the kinetics reported for human somatic differentiated cells. The expression of pluripotency markers characteristic of undifferentiated hESC was not affected by exposure to IR during the time course of our analysis. Our data on dynamics of transcriptome response of irradiated hESCs may provide a valuable tool to screen for markers of IR exposure of human cells in their most naive state; thus unmasking the key elements of DDR; at the same time, avoiding the complexity of interpreting distinct cell type-dependent genotoxic stress responses of terminally differentiated cells.

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“…Gene expression studies in human primary fibroblasts, keratinocytes (36–38) and pulmonary epithelial cells (19) suggested that growth/differentiation factor 15 ( GDF-15 ), which is also a target gene of p53, is a radiation-responsive gene. Radiation-induced alterations in GDF-15 expression are correlated with the time and dose of radiation exposure (19,34).…”

Section: Introductionmentioning

confidence: 99%

GDF-15 gene expression alterations in human lymphoblastoid cells and peripheral blood lymphocytes following exposure to ionizing radiation

Zhang

Zhang³

et al. 2017

Molecular Medicine Reports

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The identification of rapid, sensitive and high-throughput biomarkers is imperative in order to identify individuals harmed by radiation accidents, and accurately evaluate the absorbed doses of radiation. DNA microarrays have previously been used to evaluate the alterations in growth/differentiation factor 15 (GDF15) gene expression in AHH-1 human lymphoblastoid cells, following exposure to γ-rays. The present study aimed to characterize the relationship between the dose of ionizing radiation and the produced effects in GDF-15 gene expression in AHH-1 cells and human peripheral blood lymphocytes (HPBLs). GDF-15 mRNA and protein expression levels following exposure to γ-rays and neutron radiation were assessed by reverse transcription-quantitative polymerase chain reaction and western blot analysis in AHH-1 cells. In addition, alterations in GDF-15 gene expression in HPBLs following ex vivo irradiation were evaluated. The present results demonstrated that GDF-15 mRNA and protein expression levels in AHH-1 cells were significantly upregulated following exposure to γ-ray doses ranging between 1 and 10 Gy, regardless of the dose rate. A total of 48 h following exposure to neutron radiation, a dose-response relationship was identified in AHH-1 cells at γ-ray doses between 0.4 and 1.6 Gy. GDF-15 mRNA levels in HPBLs were significantly upregulated following exposure to γ-ray doses between 1 and 8 Gy, within 4–48 h following irradiation. These results suggested that significant time- and dose-dependent alterations in GDF-15 mRNA and protein expression occur in AHH-1 cells and HPBLs in the early phases following exposure to ionizing radiation. In conclusion, alterations in GDF-15 gene expression may have potential as a biomarker to evaluate radiation exposure.

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Differential Gene Expression in Primary Human Skin Keratinocytes and Fibroblasts in Response to Ionizing Radiation

Cited by 47 publications

References 56 publications

Radiation dose effect of DNA repair-related gene expression in mouse white blood cells

Radiation dose effect of DNA repair-related gene expression in mouse white blood cells

Dynamics of the transcriptome response of cultured human embryonic stem cells to ionizing radiation exposure

GDF-15 gene expression alterations in human lymphoblastoid cells and peripheral blood lymphocytes following exposure to ionizing radiation

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