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评估低剂量 X 射线照射后牙髓间充质干细胞的 DNA 损伤反应。

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

机构信息

Morphology Group, Biomedical Research Institute (BIOMED), Hasselt University, Diepenbeek, Belgium.

Belgian Nuclear Research Centre, Institute for Environment, Health and Safety, Radiobiology Unit, Mol, Belgium.

出版信息

Front Public Health. 2021 Feb 15;9:584484. doi: 10.3389/fpubh.2021.584484. eCollection 2021.

DOI:10.3389/fpubh.2021.584484
PMID:33692980
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7939020/
Abstract

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), , 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 G/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.

摘要

牙髓间充质基质细胞(MSC)中包含的干细胞对于组织内稳态至关重要。因此,确保其基因组稳定性至关重要。干细胞暴露于电离辐射(IR)中可能对正常组织内稳态有害。尽管已经确定,暴露于高剂量的电离辐射(IR)对间充质干细胞有严重的不良影响,但对低剂量 IR 的影响知之甚少。在这里,我们研究了低剂量 X 射线照射(医学成像束设置下<0.1 戈瑞;每小时 900 毫戈瑞)对乳牙牙髓干细胞、牙囊祖细胞和根尖乳头干细胞的儿童牙髓间充质基质细胞的影响。通过免疫细胞化学检测 γH2AX 和 53BP1 监测 DNA 双链断裂(DSB)的形成和修复动力学,通过流式细胞术监测细胞周期进程,通过衰老相关β-半乳糖苷酶测定法和 ELISA 监测细胞衰老。在暴露于低剂量 X 射线后,最早在辐照后 30 分钟测量到增加的 DNA DSB 修复焦点。辐照后 24 小时,DSB 数量恢复到基线水平。细胞周期分析显示,IR 对细胞周期进程只有轻微的影响,尽管在乳牙牙髓基质细胞中观察到轻微的 G2/M 期阻滞,在照射后 72 小时。尽管存在这种细胞周期阻滞,但未观察到辐射诱导的衰老。总之,低剂量 X 射线 IR(<0.1 戈瑞;每小时 900 毫戈瑞)能够诱导 DNA DSB 修复焦点数量显著增加,但细胞周期进程似乎受到最小影响。这凸显了需要对不同间充质基质细胞暴露于低剂量 IR 的影响进行更详细和广泛的研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53e8/7939020/76ded3036dcc/fpubh-09-584484-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53e8/7939020/af29614544f4/fpubh-09-584484-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53e8/7939020/e1ee0e0b4f4b/fpubh-09-584484-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53e8/7939020/a7d4469c8f8e/fpubh-09-584484-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53e8/7939020/6a647da6f759/fpubh-09-584484-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53e8/7939020/76ded3036dcc/fpubh-09-584484-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53e8/7939020/af29614544f4/fpubh-09-584484-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53e8/7939020/e1ee0e0b4f4b/fpubh-09-584484-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53e8/7939020/a7d4469c8f8e/fpubh-09-584484-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53e8/7939020/6a647da6f759/fpubh-09-584484-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53e8/7939020/76ded3036dcc/fpubh-09-584484-g0005.jpg

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