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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 RAR effect revealed by the micronucleus assay.The 0 Gy group was a sham control, without any radiation treatment. The 5 cGy and 2 Gy groups were irradiated with 5 cGy and 2 Gy doses, respectively. The (5 cGy + 2 Gy) group was irradiated with a priming dose of 5 cGy, followed by a challenging dose of 2 Gy, with a 12 h interval between application of the two doses.
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pone.0123316.g001: The RAR effect revealed by the micronucleus assay.The 0 Gy group was a sham control, without any radiation treatment. The 5 cGy and 2 Gy groups were irradiated with 5 cGy and 2 Gy doses, respectively. The (5 cGy + 2 Gy) group was irradiated with a priming dose of 5 cGy, followed by a challenging dose of 2 Gy, with a 12 h interval between application of the two doses.

Mentions: As shown in Fig 1, a low-dose irradiation (5 cGy) slightly increased the MN yield (4.77%) compared with the control (3.91%) while a high-dose irradiation (2 Gy) significantly enhanced the MN yield (9.88%). However, a priming radiation dose of 5 cGy applied at 12 h beforehand reduced the amount of chromosomal aberrations induced by the subsequent challenging dose of 2 Gy by about one third. These results were similar to those reported previously [45], and confirmed significant RAR in this cell model. As such, this cell model could be applied in microarray profiling.


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 RAR effect revealed by the micronucleus assay.The 0 Gy group was a sham control, without any radiation treatment. The 5 cGy and 2 Gy groups were irradiated with 5 cGy and 2 Gy doses, respectively. The (5 cGy + 2 Gy) group was irradiated with a priming dose of 5 cGy, followed by a challenging dose of 2 Gy, with a 12 h interval between application of the two doses.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0123316.g001: The RAR effect revealed by the micronucleus assay.The 0 Gy group was a sham control, without any radiation treatment. The 5 cGy and 2 Gy groups were irradiated with 5 cGy and 2 Gy doses, respectively. The (5 cGy + 2 Gy) group was irradiated with a priming dose of 5 cGy, followed by a challenging dose of 2 Gy, with a 12 h interval between application of the two doses.
Mentions: As shown in Fig 1, a low-dose irradiation (5 cGy) slightly increased the MN yield (4.77%) compared with the control (3.91%) while a high-dose irradiation (2 Gy) significantly enhanced the MN yield (9.88%). However, a priming radiation dose of 5 cGy applied at 12 h beforehand reduced the amount of chromosomal aberrations induced by the subsequent challenging dose of 2 Gy by about one third. These results were similar to those reported previously [45], and confirmed significant RAR in this cell model. As such, this cell model could be applied in microarray profiling.

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