计算机断层扫描对比剂对辐射诱导的基因表达和双链断裂的影响

IF 2.5 3区 医学 Q2 BIOLOGY
Simone Schüle, Felix Bunert, Carsten Hackenbroch, Meinrad Beer, Patrick Ostheim, Samantha Stewart, Matthias Port, Harry Scherthan, Michael Abend
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引用次数: 0

摘要

核事故发生后,会出现急性辐射综合征(ARS)与腹部创伤等合并伤害,可能需要造影剂增强计算机断层扫描(CT)进行诊断。在此,我们研究了碘化造影剂对辐射诱导的基因表达(GE)变化的影响,这些基因表达可用于生物模拟(AEN、BAX、CDKN1A、EDA2R、APOBEC3H)和血液学 ARS 严重程度预测(FDXR、DDB2、WNT3、POU2AF1),也可用于生物模拟的双链断裂(DSB)诱导。对 10 名健康捐献者(5 男 5 女,平均年龄:28 ± 2 岁)的全血样本进行 X 射线(0、1 和 4 Gy)照射,照射前在血液中添加或不添加碘造影剂(0.016 毫升造影剂/毫升血液)。造影剂的量设定为相当于普通患者(80 千克)在进行造影剂增强 CT 扫描时的血液浓度。照射后,血液样本在 37°C 孵育 20 分钟(DSB)和 8 小时(GE、DSB)。GE 采用定量实时聚合酶链反应进行测量。DSB 病灶由 γH2AX + 53BP1 免疫染色显示,并在大于 927 个细胞/样本中自动量化。辐射诱导的差异基因表达(DGE)和DSB灶以未添加造影剂的相应未暴露样本为参照进行计算。应用造影剂后,基因表达差异和 DSB 病灶数量均无明显变化(P = 0.07-0.94)。然而,在一些使用/不使用造影剂的 GE 和 DSB 比较中,存在微弱的显著差异(P = 0.03-0.04),但没有内在的逻辑关系,因此很可能是由于个体间的差异造成的。在核事件中,合并损伤的诊断可能需要使用碘造影剂,而根据我们的结果,碘造影剂不会改变或影响辐射诱导的 GE 变化和 DSB 病灶的数量。因此,在这种情况下,基因表达和γH2AX病灶检测仍可用于生物模拟和/或血液学ARS严重程度预测。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The Influence of Computed Tomography Contrast Agent on Radiation-Induced Gene Expression and Double-Strand Breaks.

After nuclear scenarios, combined injuries of acute radiation syndrome (ARS) with, e.g., abdominal trauma, will occur and may require contrast-enhanced computed tomography (CT) scans for diagnostic purposes. Here, we investigated the effect of iodinated contrast agents on radiation-induced gene expression (GE) changes used for biodosimetry (AEN, BAX, CDKN1A, EDA2R, APOBEC3H) and for hematologic ARS severity prediction (FDXR, DDB2, WNT3, POU2AF1), and on the induction of double-strand breaks (DSBs) used for biodosimetry. Whole blood samples from 10 healthy donors (5 males, 5 females, mean age: 28 ± 2 years) were irradiated with X rays (0, 1 and 4 Gy) with and without the addition of iodinated contrast agent (0.016 ml contrast agent/ml blood) to the blood prior to the exposure. The amount of contrast agent was set to be equivalent to the blood concentration of an average patient (80 kg) during a contrast-enhanced CT scan. After irradiation, blood samples were incubated at 37°C for 20 min (DSB) and 8 h (GE, DSB). GE was measured employing quantitative real-time polymerase chain reaction. DSB foci were revealed by γH2AX + 53BP1 immunostaining and quantified automatically in >927 cells/sample. Radiation-induced differential gene expression (DGE) and DSB foci were calculated using the respective unexposed sample without supplementation of contrast agent as the reference. Neither the GE nor the number of DSB foci was significantly (P = 0.07-0.94) altered by the contrast agent application. However, for some GE and DSB comparisons with/without contrast agent, there were weakly significant differences (P = 0.03-0.04) without an inherent logic and thus are likely due to inter-individual variation. In nuclear events, the diagnostics of combined injuries can require the use of an iodinated contrast agent, which, according to our results, does not alter or influence radiation-induced GE changes and the quantity of DSB foci. Therefore, the gene expression and γH2AX focus assay can still be applied for biodosimetry and/or hematologic ARS severity prediction in such scenarios.

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来源期刊
Radiation research
Radiation research 医学-核医学
CiteScore
5.10
自引率
8.80%
发文量
179
审稿时长
1 months
期刊介绍: Radiation Research publishes original articles dealing with radiation effects and related subjects in the areas of physics, chemistry, biology and medicine, including epidemiology and translational research. The term radiation is used in its broadest sense and includes specifically ionizing radiation and ultraviolet, visible and infrared light as well as microwaves, ultrasound and heat. Effects may be physical, chemical or biological. Related subjects include (but are not limited to) dosimetry methods and instrumentation, isotope techniques and studies with chemical agents contributing to the understanding of radiation effects.
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