Effects of therapeutic ultrasound on the nucleus and genomic DNA

Abstract

In recent years, data have been accumulating on the ability of ultrasound to affect at a distance inside the cell. Previous conceptions about therapeutic ultrasound were mainly based on compromising membrane permeability and triggering some biochemical reactions. However, it was shown that ultrasound can access deep to the nuclear territory resulting in enhanced macromolecular localization as well as alterations in gene and protein expression. Recently, we have reported on the occurrence of DNA double-strand breaks in different human cell lines exposed to ultrasound in vitro with some insight into the subsequent DNA damage response and repair pathways. The impact of these observed effects again sways between extremes. It could be advantageous if employed in gene therapy, wound and bone fracture-accelerated healing to promote cellular proliferation, or in cancer eradication if the DNA lesions would culminate in cell death. However, it could be a worrying sign if they were penultimate to further cellular adaptations to stresses and thus shaking the safety of ultrasound application in diagnosis and therapy. In this review, an overview of the rationale of therapeutic ultrasound and the salient knowledge on ultrasound-induced effects on the nucleus and genomic DNA will be presented. The implications of the findings will be discussed hopefully to provide guidance to future ultrasound research.

Application of Ultrasound in Medicine and Biotechnology

“…Although mechanical and chemical effects were implicated in this study, the addition of free radical scavengers such as DMSO or N-acetyl-L-cysteine (NAC) hardly affected the formation of gamma H2AX foci, indicating that ultrasound-induced DSB is not caused by free radicals, unlike the effect that occurs with single strand breaks (SSB) [6,7]. For decades, ultrasound has been believed to induce DNA DSB in aqueous solutions but not in cell nuclei.…”

Evaluation of the effect of ultrasonic heating and exercise heating on muscles by ultrasound elastography: An experimental clinical trial

“…US effects cell tissue via thermal, shock wave and cavitation mechanisms [8]. While high-frequency applications benefit from both thermal and mechanical effects; the heat effect occurs more at low frequencies [9]. Due to the developments such as tranducer design, more accurate measurements and calibrations of acoustic power have been accomplished, US is started to be used in physiotherapy, surgery, chemotherapy and drug delivery etc.…”

Ultrasound-mediated ocular delivery of therapeutic agents: a review

“…It can be found that damage to tissues is very dependent upon the US parameters [28]. When dealing with cavitation, it is more convenient to rely on a cavitation index then on a range of parameters such as pressure, energy, frequency which can result in various outputs due to the stochastic nature of cavitation [53] It has also been shown that US can trigger intracellular biochemical reactions and changes in gene expression [54,55] as well as DNA damage [56,57]. At the tissue level, the structure of the blood vessels can be affected [58].…”