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Effects of usEPs on DNA, Nuclear, and Subnuclear Compartments

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Ultrashort Electric Pulse Effects in Biology and Medicine

Part of the book series: Series in BioEngineering ((SERBIOENG))

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Abstract

As the largest intracellular structure in mammalian cells, the nucleus, its double phospholipid nuclear envelope, and its chromatin/DNA content were suspected targets for usEPs. Many different methods were used to determine DNA/ nuclear damage including analyses with the comet assay, DNA migration on agarose gels, mitotic indices, and chromatid structures, fluorescent in situ hybridization (FISH). In Jurkat cells exposed to (3.6 × 10−3 Vs/cm), the telomers were displaced from the nucleus, and nuclear membranes were sheared from the nucleus. SV40 fibroblasts did not show this apparent telomer and nuclear membrane damage, indicating cell-type differences., It was also shown as adherent cells were less susceptible to usEP-induced damage. Other studies showed that usEP induced significant physical damage to the nuclear membrane, cytoskeleton, and telomers, which form protein–protein or protein-DNA interactions with the nuclear envelope. Some usEP-induced nuclear/DNA damages were suspected due to effects similar to ionizing radiation caused by reactive oxygen species (ROS). Other studies using stably transfected cells with fluorescently labeled Histone-2b (H2B), which is tightly wound with DNA, and PCNA (proliferating cell nuclear antigen), which is loosely associated with DNA, indicated that H2B remained in the nucleus. In contrast, translocation of PCNA from the nucleus to the cytoplasm showed permeabilization of the nuclear membrane. So, usEPs had relatively severe and seemly rapid effects on nuclear structures. Yet, when phosphorylated Histone 2AX (γH2AX) was used as an early indicator of DNA damage in Jurkat cells, the damage appeared to be related to apoptosis's end stages since it was caspase-dependent. While all these methods are valid indicators of effects on DNA and/or the nucleus, the results between the comet assay and γH2AX under similar conditions with the same cell type are not readily reconcilable. One other study demonstrated that usEP also had effects on nuclear substructures called nuclear speckles, which are part of splicing factors and small nuclear ribonucleoproteins (snRNPs) that exhibit roles to provide splicing factors at transcription sites. So, there are apparent effects of usEPs on DNA, the nucleus, and subnuclear factors; the full extent of these effects requires additional experimentation.

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  1. Frank Reidy Research Center for Bioelectrics, Old Dominion University, Norfolk, VA, USA

    Stephen J. Beebe

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Correspondence to Stephen J. Beebe .

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Beebe, S.J. (2021). Effects of usEPs on DNA, Nuclear, and Subnuclear Compartments. In: Ultrashort Electric Pulse Effects in Biology and Medicine. Series in BioEngineering. Springer, Singapore. https://doi.org/10.1007/978-981-10-5113-5_7

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  • DOI: https://doi.org/10.1007/978-981-10-5113-5_7

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