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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 microarray analysis timeline.
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pone.0123316.g002: The microarray analysis timeline.

Mentions: The gene profiles for the single dose groups i.e., those subjected to 5 cGy (top panel of Scheme 1 in Fig 2) or 2 Gy (middle panel of Scheme 1 in Fig 2) irradiation at different time points after irradiation, at 0 (baseline), 3, 6, 12 and 24 h after irradiation were examined). Similarly, the gene profiles for the (5 cGy + 2 Gy) groups only after application of the challenging dose were examined (illustrated in the bottom panel of Scheme 1 in Fig 2). Finally, the gene profiles for the RAR groups, i.e., those subjected to a priming dose of 5 cGy applied at four different time points (viz., 0, 3, 6 and 12 h) and then subjected to a challenging dose of 2 Gy at 12 h after the priming dose, were examined, the procedures of which are shown as Scheme 2 in Fig 2.


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 microarray analysis timeline.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0123316.g002: The microarray analysis timeline.
Mentions: The gene profiles for the single dose groups i.e., those subjected to 5 cGy (top panel of Scheme 1 in Fig 2) or 2 Gy (middle panel of Scheme 1 in Fig 2) irradiation at different time points after irradiation, at 0 (baseline), 3, 6, 12 and 24 h after irradiation were examined). Similarly, the gene profiles for the (5 cGy + 2 Gy) groups only after application of the challenging dose were examined (illustrated in the bottom panel of Scheme 1 in Fig 2). Finally, the gene profiles for the RAR groups, i.e., those subjected to a priming dose of 5 cGy applied at four different time points (viz., 0, 3, 6 and 12 h) and then subjected to a challenging dose of 2 Gy at 12 h after the priming dose, were examined, the procedures of which are shown as Scheme 2 in Fig 2.

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