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超短电脉冲对神经母细胞瘤细胞系的生物学效应:能量密度的作用。

Biological effects of ultrashort electric pulses in a neuroblastoma cell line: the energy density role.

机构信息

Division of Health Protection Technologies, ENEA-Italian National Agency for New Technologies, Energy and Sustainable Economic Development, Rome, Italy.

Institut Gustave Roussy, CNRS, Metabolic and Systemic Aspects of the Oncogenesis (METSY), Université Paris-Saclay, Villejuif, France.

出版信息

Int J Radiat Biol. 2022;98(1):109-121. doi: 10.1080/09553002.2022.1998704. Epub 2021 Nov 11.

Abstract

BACKGROUND

Despite the numerous literature results about biological effects of electromagnetic field (EMF) exposure, the interaction mechanisms of these fields with organisms are still a matter of debate. Extremely low frequency (ELF) MFs can modulate redox homeostasis and we showed that 24 h exposure to 50 Hz-1 mT has a pro-oxidant effect and effects on the epigenome of SH-SY5Y cells, decreasing miR-34b/c expression through the hypermethylation of their promoter.

METHODS

Here, we investigated the role of the electromagnetic deposited energy density (ED) during exposures lasting 24 h to 1 mT amplitude MFs at a frequency of 50 Hz in inducing the above mentioned effects. To this end, we delivered ultrashort electric pulses, in the range of microsecond and nanosecond duration, with the same ED of the previously performed magnetic exposure to SH-SY5Y cells. Furthermore, we explored the effect of higher deposited energy densities. Analysis of i) gene and microRNA expression, ii) cell morphology, iii) reactive oxygen species (ROS) generation, and iv) apoptosis were carried out.

RESULTS

We observed significant changes in and expression at very low deposited ED levels, but no change of the ROS production, miR-34b/c expression, nor the appearance of indicators of apoptosis. We thus sought investigating changes in and expression caused by ultrashort electric pulses at increasing deposited ED levels. The pulses with the higher deposited ED caused cell electroporation and even other morphological changes such as cell fusion. The changes in and expression were more intense, but, again, no change of the ROS production, miR-34b/c expression, nor apoptosis induction was observed.

CONCLUSIONS

These results, showing that extremely low levels of electric stimulation (never investigated until now) can cause transcriptional changes, also reveal the safety of the electroporating pulses used in biomedical applications and open up the possibility to further therapeutic applications of this technology.

摘要

背景

尽管有大量关于电磁场(EMF)暴露的生物学效应的文献,但这些场与生物体的相互作用机制仍存在争议。极低频(ELF)MF 可以调节氧化还原稳态,我们发现 24 小时暴露于 50 Hz-1 mT 的磁场会产生促氧化作用,并影响 SH-SY5Y 细胞的表观基因组,通过其启动子的超甲基化降低 miR-34b/c 的表达。

方法

在这里,我们研究了在 50 Hz 频率下暴露于 1 mT 幅度 MF 24 小时期间,电磁能密度(ED)在诱导上述效应中的作用。为此,我们向 SH-SY5Y 细胞传递了微秒和纳秒持续时间的超短电脉冲,其 ED 与之前进行的磁暴露相同。此外,我们还研究了更高的沉积能量密度的影响。分析了 i)基因和 microRNA 表达,ii)细胞形态,iii)活性氧(ROS)生成和 iv)细胞凋亡。

结果

我们在非常低的沉积 ED 水平下观察到 和 表达的显著变化,但 ROS 生成、miR-34b/c 表达或细胞凋亡的指标没有变化。因此,我们寻求在增加沉积 ED 水平下研究超短电脉冲引起的 和 表达的变化。具有更高沉积 ED 的脉冲会导致细胞电穿孔,甚至会引起其他形态变化,如细胞融合。 和 表达的变化更为强烈,但同样,ROS 生成、miR-34b/c 表达或细胞凋亡诱导没有变化。

结论

这些结果表明,极低水平的电刺激(直到现在才进行研究)可以引起转录变化,也揭示了生物医学应用中使用的电穿孔脉冲的安全性,并为该技术的进一步治疗应用开辟了可能性。

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