DNA damage induced by Strontium-90 exposure at low concentrations in mesenchymal stromal cells: the functional consequences

Musilli, Stefania; Nicolas, Nour; Ali, Zeina El; Orellana-Moreno, P.; Grand, C. G.; Tack, Karine; Kerdine-Römer, Saadia; Bertho, Jean-Marc

doi:10.1038/srep41580

Cited by 15 publications

(11 citation statements)

References 61 publications

(77 reference statements)

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“…It has been reported before that high doses of IR can induce cellular senescence in mesenchymal stem cells ( 47 – 49 , 51 , 84 ). However, evidence of low dose IR-induced senescence is scarce ( 3 , 85 ) and contradict our data. On the other hand, there are studies that support our findings ( 74 , 86 ).…”

Section: Discussioncontrasting

confidence: 99%

In vitro Assessment of the DNA Damage Response in Dental Mesenchymal Stromal Cells Following Low Dose X-ray Exposure

Belmans

Gilles

Welkenhuysen

et al. 2021

Front. Public Health

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Stem cells contained within the dental mesenchymal stromal cell (MSC) population are crucial for tissue homeostasis. Assuring their genomic stability is therefore essential. Exposure of stem cells to ionizing radiation (IR) is potentially detrimental for normal tissue homeostasis. Although it has been established that exposure to high doses of ionizing radiation (IR) has severe adverse effects on MSCs, knowledge about the impact of low doses of IR is lacking. Here we investigated the effect of low doses of X-irradiation with medical imaging beam settings (<0.1 Gray; 900 mGray per hour), in vitro, on pediatric dental mesenchymal stromal cells containing dental pulp stem cells from deciduous teeth, dental follicle progenitor cells and stem cells from the apical papilla. DNA double strand break (DSB) formation and repair kinetics were monitored by immunocytochemistry of γH2AX and 53BP1 as well as cell cycle progression by flow cytometry and cellular senescence by senescence-associated β-galactosidase assay and ELISA. Increased DNA DSB repair foci, after exposure to low doses of X-rays, were measured as early as 30 min post-irradiation. The number of DSBs returned to baseline levels 24 h after irradiation. Cell cycle analysis revealed marginal effects of IR on cell cycle progression, although a slight G2/M phase arrest was seen in dental pulp stromal cells from deciduous teeth 72 h after irradiation. Despite this cell cycle arrest, no radiation-induced senescence was observed. In conclusion, low X-ray IR doses (< 0.1 Gray; 900 mGray per hour), were able to induce significant increases in the number of DNA DSBs repair foci, but cell cycle progression seems to be minimally affected. This highlights the need for more detailed and extensive studies on the effects of exposure to low IR doses on different mesenchymal stromal cells.

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Section: Discussioncontrasting

confidence: 99%

In vitro Assessment of the DNA Damage Response in Dental Mesenchymal Stromal Cells Following Low Dose X-ray Exposure

Belmans

Gilles

Welkenhuysen

et al. 2021

Front. Public Health

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Section: In Vitro Irradiation Of Skeletal Stem Cells Alters Differentmentioning

confidence: 99%

“…Interestingly, irradiation induced by radionucleotides, such as Strontium-90, can also induce similar effects on SSCs (15). After 7 days of exposure in vitro , a pre-osteoblast cell line showed a decreased ability to proliferate, changes in cytokine expression, and changes in their ability to support hematopoietic progenitor proliferation and differentiation (15). Exposure to Strontium-90 also showed evidence of increased senescence through increased β-galactosidase as well as senescent morphology with enlarged cytoplasm and nucleus (15).…”

Section: In Vitro Irradiation Of Skeletal Stem Cells Alters Differentmentioning

confidence: 99%

“…After 7 days of exposure in vitro , a pre-osteoblast cell line showed a decreased ability to proliferate, changes in cytokine expression, and changes in their ability to support hematopoietic progenitor proliferation and differentiation (15). Exposure to Strontium-90 also showed evidence of increased senescence through increased β-galactosidase as well as senescent morphology with enlarged cytoplasm and nucleus (15). Despite these intriguing findings in vitro, in vivo studies are necessary to determine if the same in vitro phenomena are observed.…”

Section: In Vitro Irradiation Of Skeletal Stem Cells Alters Differentmentioning

confidence: 99%

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Therapeutic Irradiation: Consequences for Bone and Bone Marrow Adipose Tissue

Costa

Reagan

2019

Front. Endocrinol.

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Radiotherapy continues to be one of the most accepted medical treatments for cancer. Localized irradiation is the most common treatment for prostate, pancreatic, rectal, cervical and endometrial malignancies. Conventional localized fractions are total doses of 30-62Gy at 1.8-2Gy per fraction, with administration of ~60Gy often used for tumor ablation. However, even the lowest dose of localized irradiation exposure can result in adverse complications to adjacent organs, tissues, and vessels, which absorb a portion of the treatment. Skeletal complications are common amongst cancer patients undergoing these localized treatments. Irradiation exposure causes deterioration to the overall quantity and quality of bone by interfering with the trabecular architecture through increased osteoclast activity and decreased osteoblast activity. Irradiation-induced bone damage parallels adipocyte infiltration of the bone marrow (BM) resulting in compositional alterations of the microenvironment that may further affect bone quality and disease state. There may also be direct effects of irradiation on the BM adipocyte/pre-adipocyte, although in vitro findings do not always agree and cellular response is dependent on irradiation dosage. Hematopoietic cells also become apoptotic upon irradiation, which causes a range of skeletal effects. Bone loss leaves patients at a greater risk for osteopenia, osteoporosis, osteonecrosis, and skeletal fractures that drastically reduce quality of life. Osteoanabolic agents stimulate bone formation and reduce fracture risk in patients with low bone density; thus, osteoanabolic or anti-resorptive agents may be useful co-treatments with irradiation. This review discusses these topics and proposes further research directions using novel or combination therapies to enhance bone health during irradiation.

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“…De plus, les lymphocytes B sont connus comme étant une population cellulaire particulièrement radiosensible (Uckun et al, 1991 ;Zarybnicka et al, 2013). Cette hypothèse est supportée par une étude récente qui montre l'induction de dommages à l'ADN et de sénescence dans des cellules stromales médullaires lorsqu'elles sont exposées in vitro au 90 Sr (Musilli et al, 2017). Ces deux études réalisées par des équipes différentes (Ghandhi et al, 2015 ;Synhaeve et al, 2016) sont donc concordantes sur le fait que la contamination interne par le 90 Sr puisse générer des modifications radio-induites significatives dans la physiologie et le fonctionnement du système immunitaire.…”

Section: Effets Du 137 Cs : éTudes Expérimentalesunclassified

Co-contaminations radiologiques et chimiques en situation post-accidentelle : données récentes et perspectives

2017

Self Cite

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Les accidents nucléaires majeurs ont conduit à la contamination de larges surfaces de terres par un mélange de radionucléides. Les populations humaines vivant actuellement sur ces territoires sont potentiellement contaminées par ingestion de radionucléides sur le long terme. Jusqu'à présent, les études se sont focalisées essentiellement sur le césium-137 ( 137 Cs), en cherchant à établir un lien entre le niveau de contamination des territoires, le niveau de contamination interne des populations et les effets biologiques observés. Cependant, des études expérimentales récentes ont montré des effets du 137 Cs chez le rongeur différents de ceux observés chez les populations contaminées. De plus, l'étude d'autres radionucléides comme le strontium-90 ( 90 Sr) montre l'induction d'effets biologiques qui pourraient en partie expliquer les observations faites chez l'Homme et attribuées à ce jour au 137 Cs. Par ailleurs, les activités industrielles et agricoles conduisent à la dispersion de polluants chimiques dont certains ont des effets toxiques bien décrits. Il en résulte que les études doivent maintenant s'intéresser à des situations d'exposition plus réalistes, avec un mélange de radionucléides et de polluants chimiques. Ceci permettra de compenser le manque de données disponibles sur les effets de mélange, de mieux comprendre les effets sanitaires observés chez les populations vivant dans des zones contaminées et d'améliorer leur protection en situation post-accidentelle.

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DNA damage induced by Strontium-90 exposure at low concentrations in mesenchymal stromal cells: the functional consequences

Cited by 15 publications

References 61 publications

In vitro Assessment of the DNA Damage Response in Dental Mesenchymal Stromal Cells Following Low Dose X-ray Exposure

In vitro Assessment of the DNA Damage Response in Dental Mesenchymal Stromal Cells Following Low Dose X-ray Exposure

Therapeutic Irradiation: Consequences for Bone and Bone Marrow Adipose Tissue

Co-contaminations radiologiques et chimiques en situation post-accidentelle : données récentes et perspectives

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