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Low dose radiation induced senescence of human mesenchymal stromal cells and impaired the autophagy process.

Alessio N, Del Gaudio S, Capasso S, Di Bernardo G, Cappabianca S, Cipollaro M, Peluso G, Galderisi U - Oncotarget (2015)

Bottom Line: Individuals may be exposed to low doses of radiation either intentionally for medical purposes or accidentally, such as those exposed to radiological terrorism or those who live near illegal radioactive waste dumpsites.We studied the effects of low dose radiation on human bone marrow mesenchymal stromal cells (MSC), which contain a subpopulation of stem cells able to differentiate in bone, cartilage, and fat; support hematopoiesis; and contribute to body's homeostasis.The main outcome of low radiation exposure, besides reduction of cell cycling, is the triggering of senescence, while the contribution to apoptosis is minimal.We hypothesize that the autophagy prevented radiation deteriorative processes, and its decline contributed to senescence.An increase in ATM staining one and six hours post-irradiation and return to basal level at 48 hours, along with persistent gamma-H2AX staining, indicated that MSC properly activated the DNA repair signaling, though some damages remained unrepaired, mainly in non-cycling cells.This suggested that the impaired DNA repair capacity of irradiated MSC seemed mainly related to the reduced activity of a non-homologous end-joining (NHEJ) system rather than HR (homologous recombination).

View Article: PubMed Central - PubMed

Affiliation: Department of Experimental Medicine, Biotechnology and Molecular Biology Section, Second University of Naples, Naples 80138, Italy.

ABSTRACT
Low doses of radiation may have profound effects on cellular function. Individuals may be exposed to low doses of radiation either intentionally for medical purposes or accidentally, such as those exposed to radiological terrorism or those who live near illegal radioactive waste dumpsites.We studied the effects of low dose radiation on human bone marrow mesenchymal stromal cells (MSC), which contain a subpopulation of stem cells able to differentiate in bone, cartilage, and fat; support hematopoiesis; and contribute to body's homeostasis.The main outcome of low radiation exposure, besides reduction of cell cycling, is the triggering of senescence, while the contribution to apoptosis is minimal. We also showed that low radiation affected the autophagic flux. We hypothesize that the autophagy prevented radiation deteriorative processes, and its decline contributed to senescence.An increase in ATM staining one and six hours post-irradiation and return to basal level at 48 hours, along with persistent gamma-H2AX staining, indicated that MSC properly activated the DNA repair signaling, though some damages remained unrepaired, mainly in non-cycling cells. This suggested that the impaired DNA repair capacity of irradiated MSC seemed mainly related to the reduced activity of a non-homologous end-joining (NHEJ) system rather than HR (homologous recombination).

No MeSH data available.


Related in: MedlinePlus

Gamma H2AX stainingFluorescence photomicrographs show the merging of cells stained with anti-H2AX (green), anti Ki-67 (red) and Hoechst 33342 (blue). A representative microscopic field for each treatment is shown. – Graph shows the degree of H2AX phosphorylation. This was evaluated by counting the number of gamma-H2AX immunofluorescent foci per cell. Foci number was determined for 200 cells. Each dot represents an individual cell. Black bars indicate mean value for each category (n = 3, *p < 0.05, **p < 0.01).
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Figure 5: Gamma H2AX stainingFluorescence photomicrographs show the merging of cells stained with anti-H2AX (green), anti Ki-67 (red) and Hoechst 33342 (blue). A representative microscopic field for each treatment is shown. – Graph shows the degree of H2AX phosphorylation. This was evaluated by counting the number of gamma-H2AX immunofluorescent foci per cell. Foci number was determined for 200 cells. Each dot represents an individual cell. Black bars indicate mean value for each category (n = 3, *p < 0.05, **p < 0.01).

Mentions: Low and high dose irradiation caused a significant augmentation of cells with a high number of gamma-H2AX foci that persisted even 48 hours post treatment (Fig. 5). Of interest, this was observed mainly in resting cells (Ki67-). This suggests that cycling cells may have a more effective DNA repair system (Fig. 5).


Low dose radiation induced senescence of human mesenchymal stromal cells and impaired the autophagy process.

Alessio N, Del Gaudio S, Capasso S, Di Bernardo G, Cappabianca S, Cipollaro M, Peluso G, Galderisi U - Oncotarget (2015)

Gamma H2AX stainingFluorescence photomicrographs show the merging of cells stained with anti-H2AX (green), anti Ki-67 (red) and Hoechst 33342 (blue). A representative microscopic field for each treatment is shown. – Graph shows the degree of H2AX phosphorylation. This was evaluated by counting the number of gamma-H2AX immunofluorescent foci per cell. Foci number was determined for 200 cells. Each dot represents an individual cell. Black bars indicate mean value for each category (n = 3, *p < 0.05, **p < 0.01).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4480742&req=5

Figure 5: Gamma H2AX stainingFluorescence photomicrographs show the merging of cells stained with anti-H2AX (green), anti Ki-67 (red) and Hoechst 33342 (blue). A representative microscopic field for each treatment is shown. – Graph shows the degree of H2AX phosphorylation. This was evaluated by counting the number of gamma-H2AX immunofluorescent foci per cell. Foci number was determined for 200 cells. Each dot represents an individual cell. Black bars indicate mean value for each category (n = 3, *p < 0.05, **p < 0.01).
Mentions: Low and high dose irradiation caused a significant augmentation of cells with a high number of gamma-H2AX foci that persisted even 48 hours post treatment (Fig. 5). Of interest, this was observed mainly in resting cells (Ki67-). This suggests that cycling cells may have a more effective DNA repair system (Fig. 5).

Bottom Line: Individuals may be exposed to low doses of radiation either intentionally for medical purposes or accidentally, such as those exposed to radiological terrorism or those who live near illegal radioactive waste dumpsites.We studied the effects of low dose radiation on human bone marrow mesenchymal stromal cells (MSC), which contain a subpopulation of stem cells able to differentiate in bone, cartilage, and fat; support hematopoiesis; and contribute to body's homeostasis.The main outcome of low radiation exposure, besides reduction of cell cycling, is the triggering of senescence, while the contribution to apoptosis is minimal.We hypothesize that the autophagy prevented radiation deteriorative processes, and its decline contributed to senescence.An increase in ATM staining one and six hours post-irradiation and return to basal level at 48 hours, along with persistent gamma-H2AX staining, indicated that MSC properly activated the DNA repair signaling, though some damages remained unrepaired, mainly in non-cycling cells.This suggested that the impaired DNA repair capacity of irradiated MSC seemed mainly related to the reduced activity of a non-homologous end-joining (NHEJ) system rather than HR (homologous recombination).

View Article: PubMed Central - PubMed

Affiliation: Department of Experimental Medicine, Biotechnology and Molecular Biology Section, Second University of Naples, Naples 80138, Italy.

ABSTRACT
Low doses of radiation may have profound effects on cellular function. Individuals may be exposed to low doses of radiation either intentionally for medical purposes or accidentally, such as those exposed to radiological terrorism or those who live near illegal radioactive waste dumpsites.We studied the effects of low dose radiation on human bone marrow mesenchymal stromal cells (MSC), which contain a subpopulation of stem cells able to differentiate in bone, cartilage, and fat; support hematopoiesis; and contribute to body's homeostasis.The main outcome of low radiation exposure, besides reduction of cell cycling, is the triggering of senescence, while the contribution to apoptosis is minimal. We also showed that low radiation affected the autophagic flux. We hypothesize that the autophagy prevented radiation deteriorative processes, and its decline contributed to senescence.An increase in ATM staining one and six hours post-irradiation and return to basal level at 48 hours, along with persistent gamma-H2AX staining, indicated that MSC properly activated the DNA repair signaling, though some damages remained unrepaired, mainly in non-cycling cells. This suggested that the impaired DNA repair capacity of irradiated MSC seemed mainly related to the reduced activity of a non-homologous end-joining (NHEJ) system rather than HR (homologous recombination).

No MeSH data available.


Related in: MedlinePlus