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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 heatmap of expressed miRNAs and Venn diagram of overlap for the three irradiation groups.The left panel shows the significantly expressed miRNAs using Bayes’ estimation in the limma package. The right panel shows the Venn plot of DEG numbers of the three groups, with green and red colors code for the numbers of down-regulated and up-regulated genes, respectively.
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pone.0123316.g008: The heatmap of expressed miRNAs and Venn diagram of overlap for the three irradiation groups.The left panel shows the significantly expressed miRNAs using Bayes’ estimation in the limma package. The right panel shows the Venn plot of DEG numbers of the three groups, with green and red colors code for the numbers of down-regulated and up-regulated genes, respectively.

Mentions: According to the previous microarray study, microRNA(s) were likely involved in irradiation-induced gene regulation. To investigate the potential microRNA(s), we made use of the irradiated samples from the 5 cGy group at 12 h post radiation, the 2 Gy group at 24 h post radiation, and the (5 cGy + 2 Gy) group at 24 h post radiation. Using Bayes’ estimation in the limma method, we found 32, 39 and 70 significantly expressed microRNAs in the 5 cGy, 2 Gy and (5 cGy + 2 Gy) groups, respectively (Fig 8). The majorities of differentially expressed microRNAs were summarized in Table 3, and were also identified by miRNA qPCR. The RT-PCR data indicated that over 83% (2 out of 24 genes and time points, e.g., hsa-miR-492 in 5 cGy and 2 Gy groups) of the ratios generated by microarray hybridizations were valid. Three microRNA databases (miRBase, TargetScan and miRGen) were used to identify the mRNAs, and to analyze the gene functions and pathways of the predicted mRNA.


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 heatmap of expressed miRNAs and Venn diagram of overlap for the three irradiation groups.The left panel shows the significantly expressed miRNAs using Bayes’ estimation in the limma package. The right panel shows the Venn plot of DEG numbers of the three groups, with green and red colors code for the numbers of down-regulated and up-regulated genes, respectively.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0123316.g008: The heatmap of expressed miRNAs and Venn diagram of overlap for the three irradiation groups.The left panel shows the significantly expressed miRNAs using Bayes’ estimation in the limma package. The right panel shows the Venn plot of DEG numbers of the three groups, with green and red colors code for the numbers of down-regulated and up-regulated genes, respectively.
Mentions: According to the previous microarray study, microRNA(s) were likely involved in irradiation-induced gene regulation. To investigate the potential microRNA(s), we made use of the irradiated samples from the 5 cGy group at 12 h post radiation, the 2 Gy group at 24 h post radiation, and the (5 cGy + 2 Gy) group at 24 h post radiation. Using Bayes’ estimation in the limma method, we found 32, 39 and 70 significantly expressed microRNAs in the 5 cGy, 2 Gy and (5 cGy + 2 Gy) groups, respectively (Fig 8). The majorities of differentially expressed microRNAs were summarized in Table 3, and were also identified by miRNA qPCR. The RT-PCR data indicated that over 83% (2 out of 24 genes and time points, e.g., hsa-miR-492 in 5 cGy and 2 Gy groups) of the ratios generated by microarray hybridizations were valid. Three microRNA databases (miRBase, TargetScan and miRGen) were used to identify the mRNAs, and to analyze the gene functions and pathways of the predicted mRNA.

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