DNA Double-Strand Breaks Induced by Cavitational Mechanical Effects of Ultrasound in Cancer Cell Lines

Ultrasonic technologies pervade the medical field: as a long established imaging modality in clinical diagnostics; and, with the emergence of targeted high intensity focused ultrasound, as a means of thermally ablating tumours. In parallel, the potential of [non-thermal] intermediate intensity ultra...

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Main Authors:	Furusawa, Yukihiro, Fujiwara, Yoshisada, Campbell, Paul, Zhao, Qing-Li, Ogawa, Ryohei, Ali Hassan, Mariame, Tabuchi, Yoshiaki, Takasaki, Ichiro, Takahashi, Akihisa, Kondo, Takashi
Format:	Online
Language:	English
Published:	Public Library of Science 2012
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3250400/

id	pubmed-3250400
recordtype	oai_dc
spelling	pubmed-32504002012-01-10 DNA Double-Strand Breaks Induced by Cavitational Mechanical Effects of Ultrasound in Cancer Cell Lines Furusawa, Yukihiro Fujiwara, Yoshisada Campbell, Paul Zhao, Qing-Li Ogawa, Ryohei Ali Hassan, Mariame Tabuchi, Yoshiaki Takasaki, Ichiro Takahashi, Akihisa Kondo, Takashi Research Article Ultrasonic technologies pervade the medical field: as a long established imaging modality in clinical diagnostics; and, with the emergence of targeted high intensity focused ultrasound, as a means of thermally ablating tumours. In parallel, the potential of [non-thermal] intermediate intensity ultrasound as a minimally invasive therapy is also being rigorously assessed. Here, induction of apoptosis in cancer cells has been observed, although definitive identification of the underlying mechanism has thus far remained elusive. A likely candidate process has been suggested to involve sonochemical activity, where reactive oxygen species (ROS) mediate the generation of DNA single-strand breaks. Here however, we provide compelling new evidence that strongly supports a purely mechanical mechanism. Moreover, by a combination of specific assays (neutral comet tail and staining for γH2AX foci formation) we demonstrate for the first time that US exposure at even moderate intensities exhibits genotoxic potential, through its facility to generate DNA damage across multiple cancer lines. Notably, colocalization assays highlight that ionizing radiation and ultrasound have distinctly different signatures to their respective γH2AX foci formation patterns, likely reflecting the different stress distributions that initiated damage formation. Furthermore, parallel immuno-blotting suggests that DNA-PKcs have a preferential role in the repair of ultrasound-induced damage. Public Library of Science 2012-01-03 /pmc/articles/PMC3250400/ /pubmed/22235259 http://dx.doi.org/10.1371/journal.pone.0029012 Text en Furusawa et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Furusawa, Yukihiro Fujiwara, Yoshisada Campbell, Paul Zhao, Qing-Li Ogawa, Ryohei Ali Hassan, Mariame Tabuchi, Yoshiaki Takasaki, Ichiro Takahashi, Akihisa Kondo, Takashi
spellingShingle	Furusawa, Yukihiro Fujiwara, Yoshisada Campbell, Paul Zhao, Qing-Li Ogawa, Ryohei Ali Hassan, Mariame Tabuchi, Yoshiaki Takasaki, Ichiro Takahashi, Akihisa Kondo, Takashi DNA Double-Strand Breaks Induced by Cavitational Mechanical Effects of Ultrasound in Cancer Cell Lines
author_facet	Furusawa, Yukihiro Fujiwara, Yoshisada Campbell, Paul Zhao, Qing-Li Ogawa, Ryohei Ali Hassan, Mariame Tabuchi, Yoshiaki Takasaki, Ichiro Takahashi, Akihisa Kondo, Takashi
author_sort	Furusawa, Yukihiro
title	DNA Double-Strand Breaks Induced by Cavitational Mechanical Effects of Ultrasound in Cancer Cell Lines
title_short	DNA Double-Strand Breaks Induced by Cavitational Mechanical Effects of Ultrasound in Cancer Cell Lines
title_full	DNA Double-Strand Breaks Induced by Cavitational Mechanical Effects of Ultrasound in Cancer Cell Lines
title_fullStr	DNA Double-Strand Breaks Induced by Cavitational Mechanical Effects of Ultrasound in Cancer Cell Lines
title_full_unstemmed	DNA Double-Strand Breaks Induced by Cavitational Mechanical Effects of Ultrasound in Cancer Cell Lines
title_sort	dna double-strand breaks induced by cavitational mechanical effects of ultrasound in cancer cell lines
description	Ultrasonic technologies pervade the medical field: as a long established imaging modality in clinical diagnostics; and, with the emergence of targeted high intensity focused ultrasound, as a means of thermally ablating tumours. In parallel, the potential of [non-thermal] intermediate intensity ultrasound as a minimally invasive therapy is also being rigorously assessed. Here, induction of apoptosis in cancer cells has been observed, although definitive identification of the underlying mechanism has thus far remained elusive. A likely candidate process has been suggested to involve sonochemical activity, where reactive oxygen species (ROS) mediate the generation of DNA single-strand breaks. Here however, we provide compelling new evidence that strongly supports a purely mechanical mechanism. Moreover, by a combination of specific assays (neutral comet tail and staining for γH2AX foci formation) we demonstrate for the first time that US exposure at even moderate intensities exhibits genotoxic potential, through its facility to generate DNA damage across multiple cancer lines. Notably, colocalization assays highlight that ionizing radiation and ultrasound have distinctly different signatures to their respective γH2AX foci formation patterns, likely reflecting the different stress distributions that initiated damage formation. Furthermore, parallel immuno-blotting suggests that DNA-PKcs have a preferential role in the repair of ultrasound-induced damage.
publisher	Public Library of Science
publishDate	2012
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3250400/
_version_	1611497918849613824

DNA Double-Strand Breaks Induced by Cavitational Mechanical Effects of Ultrasound in Cancer Cell Lines

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