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外周血细胞离体暴露于各种 CT 光子能谱后基因表达的变化和 DNA 损伤。

Gene expression changes and DNA damage after ex vivo exposure of peripheral blood cells to various CT photon spectra.

机构信息

Bundeswehr Institute of Radiobiology Affiliated to Ulm University, Neuherbergstrasse 11, 80937, Munich, Germany.

Department of Radiology, Bundeswehr Central Hospital Koblenz, Rübenacher Straße 170, 56072, Koblenz, Germany.

出版信息

Sci Rep. 2021 Jun 8;11(1):12060. doi: 10.1038/s41598-021-91023-7.

DOI:10.1038/s41598-021-91023-7
PMID:34103547
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8187728/
Abstract

Dual-energy CT provides enhanced diagnostic power with similar or even reduced radiation dose as compared to single-energy CT. Its principle is based on the distinct physical properties of low and high energetic photons, which, however, may also affect the biological effectiveness and hence the extent of CT-induced cellular damage. Therefore, a comparative analysis of biological effectiveness of dual- and single-energy CT scans with focus on early gene regulation and frequency of radiation-induced DNA double strand breaks (DSBs) was performed. Blood samples from three healthy individuals were irradiated ex vivo with single-energy (80 kV and 150 kV) and dual-energy tube voltages (80 kV/Sn150kV) employing a modern dual source CT scanner resulting in Volume Computed Tomography Dose Index (CTDIvol) of 15.79-18.26 mGy and dose length product (DLP) of 606.7-613.8 mGy*cm. Non-irradiated samples served as a control. Differential gene expression in peripheral blood mononuclear cells was analyzed 6 h after irradiation using whole transcriptome sequencing. DSB frequency was studied by 53BP1 + γH2AX co-immunostaining and microscopic evaluation of their focal accumulation at DSBs. Neither the analysis of gene expression nor DSB frequency provided any evidence for significantly increased biological effectiveness of dual-energy CT in comparison to samples irradiated with particular single-energy CT spectra. Relative to control, irradiated samples were characterized by a significantly higher rate of DSBs (p < 0.001) and the shared upregulation of five genes, AEN, BAX, DDB2, FDXR and EDA2R, which have already been suggested as radiation-induced biomarkers in previous studies. Despite steadily decreasing doses, CT diagnostics remain a genotoxic stressor with impact on gene regulation and DNA integrity. However, no evidence was found that varying X-ray spectra of CT impact the extent of cellular damage.

摘要

双能 CT 提供了增强的诊断能力,与单能 CT 相比,其辐射剂量相似甚至更低。其原理基于低能和高能光子的不同物理特性,然而,这也可能影响生物效应,从而影响 CT 诱导的细胞损伤程度。因此,我们对双能和单能 CT 扫描的生物效应进行了比较分析,重点关注早期基因调控和辐射诱导的 DNA 双链断裂(DSB)的频率。从三名健康个体中采集血液样本,在体外使用现代双源 CT 扫描仪用单能(80kV 和 150kV)和双能管电压(80kV/Sn150kV)进行照射,得到的容积 CT 剂量指数(CTDIvol)为 15.79-18.26mGy,剂量长度乘积(DLP)为 606.7-613.8mGy*cm。未照射的样本作为对照。照射后 6 小时,使用全转录组测序分析外周血单核细胞中的差异基因表达。通过 53BP1+γH2AX 共免疫染色和 DSB 焦点积累的显微镜评估研究 DSB 频率。基因表达分析和 DSB 频率均未显示出双能 CT 比用特定单能 CT 谱照射的样本具有明显更高的生物效应。与对照相比,照射的样本具有明显更高的 DSB 率(p<0.001)和五个基因的共同上调,AEN、BAX、DDB2、FDXR 和 EDA2R,这些基因在以前的研究中已被认为是辐射诱导的生物标志物。尽管剂量不断降低,但 CT 诊断仍然是一种具有遗传毒性的应激源,会影响基因调控和 DNA 完整性。然而,没有证据表明 CT 的 X 射线谱变化会影响细胞损伤的程度。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ffb/8187728/d6ccbe080f3a/41598_2021_91023_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ffb/8187728/d0093f680e14/41598_2021_91023_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ffb/8187728/55381d1fd424/41598_2021_91023_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ffb/8187728/d6ccbe080f3a/41598_2021_91023_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ffb/8187728/d0093f680e14/41598_2021_91023_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ffb/8187728/7bd230666ad4/41598_2021_91023_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ffb/8187728/e2fb0e0b67f0/41598_2021_91023_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ffb/8187728/55381d1fd424/41598_2021_91023_Fig4_HTML.jpg
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