AbstractAs patient exposure to ionizing radiation from medical imaging and its risks are continuing issues, this study aimed to evaluate DNA damage and repair markers after myocardial perfusion single-photon emission computed tomography (MPS). Thirty-two patients undergoing Tc-99m sestamibi MPS were studied.

摘要由于患者暴露于医学成像的电离辐射及其风险仍然存在，本研究旨在评估心肌灌注单光子发射计算机断层扫描（MPS）后的DNA损伤和修复标志物。研究了32名接受Tc-99m sestamibi MPS治疗的患者。

Peripheral blood was collected before radiotracer injection at rest and 60–90 min after injection. The comet assay (single-cell gel electrophoresis) was performed with peripheral blood cells to detect DNA strand breaks. Three descriptors were evaluated: the percentage of DNA in the comet tail, tail length, and tail moment (the product of DNA tail percentage and tail length).

在放射性示踪剂注射前和注射后60-90分钟收集外周血。用外周血细胞进行彗星试验（单细胞凝胶电泳）以检测DNA链断裂。评估了三个描述符：彗星尾巴中DNA的百分比，尾巴长度和尾矩（DNA尾巴百分比和尾巴长度的乘积）。

Quantitative PCR (qPCR) was performed to evaluate the expression of five genes related to signaling pathways in response to DNA damage and repair (ATM, ATR, BRCA1, CDKN1A, and XPC). Mann–Whitney’s test was employed for statistical analysis; p < 0.05 was considered significant. Mean Tc-99m sestamibi dose was 15.1 mCi.

进行定量PCR（qPCR）以评估响应DNA损伤和修复的与信号传导途径相关的五个基因（ATM，ATR，BRCA1，CDKN1A和XPC）的表达。Mann-Whitney检验用于统计分析；p<0.05被认为是显着的。Tc-99m sestamibi的平均剂量为15.1 mCi。

After radiotracer injection, comparing post-exposure to pre-exposure samples of each of the 32 patients, no statistically significant differences of the DNA percentage in the tail, tail length or tail moment were found. qPCR revealed increased expression of BRCA1 and XPC, without any significant difference regarding the other genes.

放射性示踪剂注射后，将32名患者的暴露后和暴露前样本进行比较，发现尾巴中的DNA百分比，尾巴长度或尾巴力矩没有统计学上的显着差异。qPCR显示BRCA1和XPC的表达增加，而其他基因没有任何显着差异。

No significant increase in DNA strand breaks was detected after a single radiotracer injection for MPS. There was activation of only two repair genes, which may indicate that, in the current patient sample, the effects of ionizing radiation on the DNA were not large enough to trigger intense repair responses, suggesting the absence of significant DNA damage..

单次放射性示踪剂注射MPS后，未检测到DNA链断裂的显着增加。只有两个修复基因被激活，这可能表明，在当前的患者样本中，电离辐射对DNA的影响不足以引发强烈的修复反应，这表明没有明显的DNA损伤。。

IntroductionDue to its central role in the diagnostic and prognostic evaluation of coronary artery disease, myocardial perfusion imaging with single photon emission-computed tomography (MPS) is one of the most frequently performed noninvasive cardiac imaging tests, generating concern about the potentially excessive radiation exposure for patients, including the cumulative doses of lifetime radiation, even though the individual levels of radiation exposure are considered low1,2.The understanding of the biological effects of low-dose radiation exposure is challenging.

引言由于其在冠状动脉疾病的诊断和预后评估中的核心作用，单光子发射计算机断层扫描（MPS）的心肌灌注成像是最常进行的无创心脏成像测试之一，引起人们对患者潜在过度辐射暴露的担忧，包括终生辐射的累积剂量，即使个体辐射暴露水平被认为较低1,2。对低剂量辐射暴露的生物学效应的理解具有挑战性。

Most knowledge is derived from high-dose exposure, with the linear no-threshold (LNT) model definition that radiation risk is directly proportional to dose, and therefore any amount of radiation, even small, is potentially harmful. However, the validity of the LNT in the context of low radiation doses has been questioned2,3.

大多数知识来自高剂量暴露，线性无阈值（LNT）模型定义辐射风险与剂量成正比，因此任何辐射量，即使很小，也可能有害。然而，LNT在低辐射剂量情况下的有效性受到质疑2,3。

Our group has verified that, after radiotracer injection for MPS, increased DNA fragmentation occurred, even though severe levels of damage were the least frequent4. With changes in imaging protocols that have led to a reduction of injected radiotracer doses, a re-evaluation of the genotoxic effects of ionizing radiation is desirable.

我们小组已经证实，在放射性示踪剂注射MPS后，DNA片段化增加，即使严重程度的损伤是最不常见的4。随着成像方案的改变导致注射放射性示踪剂剂量的减少，需要重新评估电离辐射的遗传毒性作用。

Furthermore, it is known that in response to DNA damage, cells activate proteins and genes involved in apoptosis, DNA repair, cell cycle regulation, and chromatin remodeling, a process collectively known as the “DNA damage response” pathways5. The extent to which these pathways are activated may represent how patients respond to radiation exposure.

此外，已知响应DNA损伤，细胞激活参与细胞凋亡，DNA修复，细胞周期调节和染色质重塑的蛋白质和基因，这一过程统称为“DNA损伤反应”途径5。这些途径被激活的程度可能代表患者对辐射暴露的反应。

This study sought to evaluate whether low dose radiation exposure from MPS induced DNA damage and the activation of repair pathways.MethodsPatients ≥ 18 years undergoing MPS were considered eligible for the study.

这项研究试图评估MPS的低剂量辐射暴露是否诱导DNA损伤和修复途径的激活。方法接受MPS治疗≥18年的患者被认为符合研究条件。

Data availability

数据可用性

The datasets used and/or analysed during the current study available from the corresponding author on reasonable request.

本研究中使用和/或分析的数据集可根据合理要求从通讯作者处获得。

AbbreviationsACEi:

缩写ACEi：

Angiotensin-converting enzyme inhibitors

血管紧张素转换酶抑制剂

ARB:

ARB：

Angiotensin receptor blockers

血管紧张素受体阻滞剂

ATM:

ATM：

Ataxia telangiectasia mutated. Serine/threonine protein kinase

共济失调毛细血管扩张突变。丝氨酸/苏氨酸蛋白激酶

ATR:

自动条码读取器：

Ataxia telangiectasia and Rad3-related protein

共济失调毛细血管扩张症和Rad3相关蛋白

BRCA1:

BRCA1：

Breast cancer 1

乳腺癌1

CABG:

CABG：

Coronary artery bypass grafting

冠状动脉旁路移植术

CDKN1A:

CDKN1A：

Cyclin dependent kinase inhibitor 1A

细胞周期蛋白依赖性激酶抑制剂1A

DMSA:

DMSA：

Dimercaptosuccinic acid

二巯基琥珀酸

EDTA:

EDTA：

Ethylenediaminetetraacetic acid

乙二胺四乙酸

GAPDH:

GAPDH:

Glyceraldehyde 3-phosphate dehydrogenase

甘油醛3-磷酸脱氢酶

MPS:

议员：

Myocardial perfusion single-photon emission computed tomography

心肌灌注单光子发射计算机断层扫描

NCRP:

NCRP：

National council on radiation protection and measurements

国家辐射防护和测量委员会

PCI:

PCI（PCI）：

Percutaneous transluminal coronary angioplasty

经皮冠状动脉腔内成形术

XPC:

XPC：

Xeroderma pigmentosum, complementation group C

色素性干皮病，互补组C

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IFMBE Proceedings, vol 14 (eds. Magjarevic, R., Nagel, J.H.) (Springer, 2006). https://doi.org/10.1007/978-3-540-36841-0_7.Download referencesAcknowledgementsThe authors thank Adriana Xavier de Brito, MD, PhD, for support at the Nuclear Medicine Laboratory, and Paola Negri Fernandes, MSc, for aiding to perform the analyses.FundingThis work was supported by the FAPERJ (Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro), Grant number 200.889/2021.Author informationAuthors and AffiliationsCoordenação de Ensino e Pesquisa, Instituto Nacional de Cardiologia, R.

IFMBE论文集，第14卷（Magjarevic，R.，Nagel，J.H.编辑）（施普林格，2006年）。https://doi.org/10.1007/978-3-540-36841-0_7.Download参考文献鸣谢作者感谢医学博士Adriana Xavier de Brito在核医学实验室的支持，以及理学硕士Paola Negri Fernandes帮助进行分析。基金会这项工作得到了巴西心脏病研究所的支持（基金会），拨款号为200.889/2021。作者信息作者和附属机构。

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PubMed Google ScholarContributionsMaterial preparation, data collection and analysis were performed by M.C.F., A.P.A., F.R. and G.D.M. Study conception and design, as well as the first draft of the manuscript, were performed by A.D.L. All authors commented on the versions of the manuscript.

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Reprints and permissionsAbout this articleCite this articleDe Lorenzo, A., dos Santos Fernandes, M.C., Romeiro, F. et al. DNA damage and repair in patients undergoing myocardial perfusion single-photon emission computed tomography.

转载和许可本文引用本文de Lorenzo，A.，dos Santos Fernandes，M.C.，Romeiro，F。等人。接受心肌灌注单光子发射计算机断层扫描的患者的DNA损伤和修复。

Sci Rep 14, 13079 (2024). https://doi.org/10.1038/s41598-024-63537-3Download citationReceived: 21 February 2024Accepted: 29 May 2024Published: 07 June 2024DOI: https://doi.org/10.1038/s41598-024-63537-3Share this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard.

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KeywordsMyocardial perfusion imagingRadiationComet assayDNA

关键词心肌灌注成像梯度彗星试验DNA

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