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Gene profiling characteristics of radioadaptive response in AG01522 normal human fibroblasts.

Hou J, Wang F, Kong P, Yu PK, Wang H, Han W - PLoS ONE (2015)

Bottom Line: Despite the completion of numerous experimental studies on RAR, the underlying mechanism has remained unclear.In this study, we aimed to have a comprehensive investigation on the RAR induced in the AG01522 human fibroblasts first exposed to 5 cGy (priming dose) and then followed by 2 Gy (challenge dose) of X-ray through comparisons to those cells that had only received a single 2 Gy dose.We conclude that RAR benefits from the alarm mechanisms triggered by a low-dose priming radation dose.

View Article: PubMed Central - PubMed

Affiliation: Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, China.

ABSTRACT
Radioadaptive response (RAR) in mammalian cells refers to the phenomenon where a low-dose ionizing irradiation alters the gene expression profiles, and protects the cells from the detrimental effects of a subsequent high dose exposure. Despite the completion of numerous experimental studies on RAR, the underlying mechanism has remained unclear. In this study, we aimed to have a comprehensive investigation on the RAR induced in the AG01522 human fibroblasts first exposed to 5 cGy (priming dose) and then followed by 2 Gy (challenge dose) of X-ray through comparisons to those cells that had only received a single 2 Gy dose. We studied how the priming dose affected the expression of gene transcripts, and to identify transcripts or pathways that were associated with the reduced chromosomal damages (in terms of the number of micronuclei) after application of the challenging dose. Through the mRNA and microRNA microarray analyses, the transcriptome alteration in AG01522 cells was examined, and the significantly altered genes were identified for different irradiation procedures using bioinformatics approaches. We observed that a low-dose X-ray exposure produced an alert, triggering and altering cellular responses to defend against subsequent high dose-induced damages, and accelerating the cell repair process. Moreover, the p53 signaling pathway was found to play critial roles in regulating DNA damage responses at the early stage after application of the challenging dose, particularly in the RAR group. Furthermore, microRNA analyses also revealed that cell communication and intercellular signaling transduction played important roles after low-dose irradiation. We conclude that RAR benefits from the alarm mechanisms triggered by a low-dose priming radation dose.

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The pie charts showing the predicted mRNA enrichment GO terms for the three irradiation groups.The mRNAs predicted using three microRNA databases were input into ClueGO plugged in Cytoscape for enrichment analysis for gene ontology. The Cellular Component, Biological Process, Molecular Function and Immune System Process GO terms were selected for this analysis. The two-sided hypergeometric test was used in the statistical inference, and the Benjamini-Hochberg method was applied in p value correlation. The adjusted p-value threshold was set to 0.001.
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pone.0123316.g009: The pie charts showing the predicted mRNA enrichment GO terms for the three irradiation groups.The mRNAs predicted using three microRNA databases were input into ClueGO plugged in Cytoscape for enrichment analysis for gene ontology. The Cellular Component, Biological Process, Molecular Function and Immune System Process GO terms were selected for this analysis. The two-sided hypergeometric test was used in the statistical inference, and the Benjamini-Hochberg method was applied in p value correlation. The adjusted p-value threshold was set to 0.001.

Mentions: When we compared the mRNA GO terms predicted for the three groups, the low-dose 5 cGy group showed that most GO terms focused on cell communication, intracellular signal transduction and system development (Fig 9). Meanwhile, the enrichment pathway also indicated that these predicted mRNAs were dominnat in translation, chromosome maintenance, meiotic recombination and Wnt signaling pathways and other metabolic pathways or terms (Fig 9). On the other hand, however, a high-dose (2 Gy) radiation induced many genes involved in regulation of cellular processes and primary metabolic processes, multicellular organismal development and regualtion of signaling (Fig 9). These were also confirmed by the pathway results (S10 Fig). The more notable results were the EGFR pathway, eukaryotic translation elongation and RNA process, metabolism of vitamins and cofactors, calcium and Wnt signaling pathways (S11 Fig). The RAR group, with 5 cGy priming dose and 2 Gy changelling dose, showed that the GO results were most likely a combination of the individual results for the 5 cGy and 2 Gy groups. It combined both of their GO terms, comprising cell communication, intracellular siganl transduction, including most of the enriched results for the 5 cGy case, and also regulation of cellular processes for the 2 Gy group. Furthermore, the enrichment results also showed complicated pathways, including EGFR signaling, insulin signaling, exon junction complex, metabolic and RNA and DNA processes (S12 Fig).


Gene profiling characteristics of radioadaptive response in AG01522 normal human fibroblasts.

Hou J, Wang F, Kong P, Yu PK, Wang H, Han W - PLoS ONE (2015)

The pie charts showing the predicted mRNA enrichment GO terms for the three irradiation groups.The mRNAs predicted using three microRNA databases were input into ClueGO plugged in Cytoscape for enrichment analysis for gene ontology. The Cellular Component, Biological Process, Molecular Function and Immune System Process GO terms were selected for this analysis. The two-sided hypergeometric test was used in the statistical inference, and the Benjamini-Hochberg method was applied in p value correlation. The adjusted p-value threshold was set to 0.001.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4401551&req=5

pone.0123316.g009: The pie charts showing the predicted mRNA enrichment GO terms for the three irradiation groups.The mRNAs predicted using three microRNA databases were input into ClueGO plugged in Cytoscape for enrichment analysis for gene ontology. The Cellular Component, Biological Process, Molecular Function and Immune System Process GO terms were selected for this analysis. The two-sided hypergeometric test was used in the statistical inference, and the Benjamini-Hochberg method was applied in p value correlation. The adjusted p-value threshold was set to 0.001.
Mentions: When we compared the mRNA GO terms predicted for the three groups, the low-dose 5 cGy group showed that most GO terms focused on cell communication, intracellular signal transduction and system development (Fig 9). Meanwhile, the enrichment pathway also indicated that these predicted mRNAs were dominnat in translation, chromosome maintenance, meiotic recombination and Wnt signaling pathways and other metabolic pathways or terms (Fig 9). On the other hand, however, a high-dose (2 Gy) radiation induced many genes involved in regulation of cellular processes and primary metabolic processes, multicellular organismal development and regualtion of signaling (Fig 9). These were also confirmed by the pathway results (S10 Fig). The more notable results were the EGFR pathway, eukaryotic translation elongation and RNA process, metabolism of vitamins and cofactors, calcium and Wnt signaling pathways (S11 Fig). The RAR group, with 5 cGy priming dose and 2 Gy changelling dose, showed that the GO results were most likely a combination of the individual results for the 5 cGy and 2 Gy groups. It combined both of their GO terms, comprising cell communication, intracellular siganl transduction, including most of the enriched results for the 5 cGy case, and also regulation of cellular processes for the 2 Gy group. Furthermore, the enrichment results also showed complicated pathways, including EGFR signaling, insulin signaling, exon junction complex, metabolic and RNA and DNA processes (S12 Fig).

Bottom Line: Despite the completion of numerous experimental studies on RAR, the underlying mechanism has remained unclear.In this study, we aimed to have a comprehensive investigation on the RAR induced in the AG01522 human fibroblasts first exposed to 5 cGy (priming dose) and then followed by 2 Gy (challenge dose) of X-ray through comparisons to those cells that had only received a single 2 Gy dose.We conclude that RAR benefits from the alarm mechanisms triggered by a low-dose priming radation dose.

View Article: PubMed Central - PubMed

Affiliation: Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, China.

ABSTRACT
Radioadaptive response (RAR) in mammalian cells refers to the phenomenon where a low-dose ionizing irradiation alters the gene expression profiles, and protects the cells from the detrimental effects of a subsequent high dose exposure. Despite the completion of numerous experimental studies on RAR, the underlying mechanism has remained unclear. In this study, we aimed to have a comprehensive investigation on the RAR induced in the AG01522 human fibroblasts first exposed to 5 cGy (priming dose) and then followed by 2 Gy (challenge dose) of X-ray through comparisons to those cells that had only received a single 2 Gy dose. We studied how the priming dose affected the expression of gene transcripts, and to identify transcripts or pathways that were associated with the reduced chromosomal damages (in terms of the number of micronuclei) after application of the challenging dose. Through the mRNA and microRNA microarray analyses, the transcriptome alteration in AG01522 cells was examined, and the significantly altered genes were identified for different irradiation procedures using bioinformatics approaches. We observed that a low-dose X-ray exposure produced an alert, triggering and altering cellular responses to defend against subsequent high dose-induced damages, and accelerating the cell repair process. Moreover, the p53 signaling pathway was found to play critial roles in regulating DNA damage responses at the early stage after application of the challenging dose, particularly in the RAR group. Furthermore, microRNA analyses also revealed that cell communication and intercellular signaling transduction played important roles after low-dose irradiation. We conclude that RAR benefits from the alarm mechanisms triggered by a low-dose priming radation dose.

Show MeSH
Related in: MedlinePlus