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Apoptotic and genotoxic effects of low-intensity ultrasound on healthy and leukemic human peripheral mononuclear blood cells

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Abstract

Purpose

To scrutinize the apoptotic and genotoxic effects of low-intensity ultrasound and an ultrasound contrast agent (SonoVue; Bracco Diagnostics Inc., EU) on human peripheral mononuclear blood cells (PMBCs).

Methods

PMBCs were subjected to a low-intensity ultrasound field (1-MHz frequency; spatial peak temporal average intensity 0.18 W/cm2) followed by analysis for apoptosis and DNA damage (single-strand breaks + double-strand breaks). The comet assay was then repeated after 2 h to examine the ability of cells to repair DNA breaks.

Results

The results demonstrated that low-intensity ultrasound was capable of selectively inducing apoptosis in leukemic PMBCs, but not in healthy cells. The introduction of ultrasound contrast agent SonoVue resulted in an increase in apoptosis in both groups. DNA analysis after ultrasound exposure indicated that ultrasound triggered DNA damage in leukemic PMBCs (66.05 ± 13.36%), while the damage was minimal (7.01 ± 0.89%) in control PMBCs. However, both cell lines demonstrated an ability to repair DNA single- and double-strand breaks 2 h after sonication.

Conclusions

The study demonstrated that low-intensity ultrasound selectively induced apoptosis in cancer PMBCs. Ultrasound-induced DNA damage was observed primarily in leukemic PMBCs. Nevertheless, both cell lines were able to repair ultrasound-mediated DNA strand breaks.

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Acknowledgements

The study was supported through the Grant “Induction of apoptosis by low-intensity ultrasound for cancer therapy” (Programme 055 “Scientific and technical activities”; sub-programme 100 “Programme-targeted funding” 2014–2017; Government of Republic of Kazakhstan). Special thanks to Sholpan Kauanova and Dr. Loreto B. Feril, Jr. for help with preparing the manuscript.

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Correspondence to Timur Saliev.

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Conflict of interest

Timur Saliev declares that he has no conflict of interest. Dinara Begimbetova declares that she has no conflict of interest. Dinara Baiskhanova declares that she has no conflict of interest. Danysh Abetov declares that he has no conflict of interest. Ulykbek Kairov declares that he has no conflict of interest. Charles P. Gilman declares that he has no conflict of interest. Bakhyt Matkarimov declares that he has no conflict of interest. Katsuro Tachibana declares that he has no conflict of interest.

Ethical statements

All protocols pertaining to human subjects were first approved by Nazarbayev University’s Institutional Research Ethics Committee, Astana, Kazakhstan.

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Saliev, T., Begimbetova, D., Baiskhanova, D. et al. Apoptotic and genotoxic effects of low-intensity ultrasound on healthy and leukemic human peripheral mononuclear blood cells. J Med Ultrasonics 45, 31–39 (2018). https://doi.org/10.1007/s10396-017-0805-6

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  • DOI: https://doi.org/10.1007/s10396-017-0805-6

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