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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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Related in: MedlinePlus

The pathway enrichment analysis results of the 2 Gy group at different time points.The KEGG, REACTOME and WikiPathways databases in ClueGO were employed for pathway enrichment analysis of each differential group gene sets acquired from microarray analyses. The Enrichment/Depletion was tested by the two-side hypergeometric test, and the Benjamini and Hochberg false-discovery rate was set to 0.05. The green and red colors code for down-regulation and up-regulation of genes, respectively, in each group.
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pone.0123316.g006: The pathway enrichment analysis results of the 2 Gy group at different time points.The KEGG, REACTOME and WikiPathways databases in ClueGO were employed for pathway enrichment analysis of each differential group gene sets acquired from microarray analyses. The Enrichment/Depletion was tested by the two-side hypergeometric test, and the Benjamini and Hochberg false-discovery rate was set to 0.05. The green and red colors code for down-regulation and up-regulation of genes, respectively, in each group.

Mentions: The high radiation dose (2 Gy) led to different cellular responses. At the early stage, most up-regulated genes were involved in G protein-coupled receptors (GPCR) downstream signaling, cytokine-cytokine receptor interaction and interferon gamma signaling pathway at 3 h post irradiation. As early as 6 h post irradiation, some genes were involved in promotion of the p53 signaling pathway and responded to DNA damages, either through apoptosis or miRNA, and also slowed down cell replication via controlling cell cycle checkpoints. At later time points from 12 to 24 h post irradiation, more and more resources were spent on the negative regulation of DNA replication and cell cycle, particularly at 24 h post irradiation, and the DNA double-strand break repair term indicated repair in order to rescue the cells from the X-ray induced damages (data shown in Fig 6).


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 pathway enrichment analysis results of the 2 Gy group at different time points.The KEGG, REACTOME and WikiPathways databases in ClueGO were employed for pathway enrichment analysis of each differential group gene sets acquired from microarray analyses. The Enrichment/Depletion was tested by the two-side hypergeometric test, and the Benjamini and Hochberg false-discovery rate was set to 0.05. The green and red colors code for down-regulation and up-regulation of genes, respectively, in each group.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0123316.g006: The pathway enrichment analysis results of the 2 Gy group at different time points.The KEGG, REACTOME and WikiPathways databases in ClueGO were employed for pathway enrichment analysis of each differential group gene sets acquired from microarray analyses. The Enrichment/Depletion was tested by the two-side hypergeometric test, and the Benjamini and Hochberg false-discovery rate was set to 0.05. The green and red colors code for down-regulation and up-regulation of genes, respectively, in each group.
Mentions: The high radiation dose (2 Gy) led to different cellular responses. At the early stage, most up-regulated genes were involved in G protein-coupled receptors (GPCR) downstream signaling, cytokine-cytokine receptor interaction and interferon gamma signaling pathway at 3 h post irradiation. As early as 6 h post irradiation, some genes were involved in promotion of the p53 signaling pathway and responded to DNA damages, either through apoptosis or miRNA, and also slowed down cell replication via controlling cell cycle checkpoints. At later time points from 12 to 24 h post irradiation, more and more resources were spent on the negative regulation of DNA replication and cell cycle, particularly at 24 h post irradiation, and the DNA double-strand break repair term indicated repair in order to rescue the cells from the X-ray induced damages (data shown in Fig 6).

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