DNA double-strand breaks induced by cavitational mechanical effects of ultrasound in cancer cell lines

Yukihiro Furusawa, Yoshisada Fujiwara, Paul Campbell, Qing Li Zhao, Ryohei Ogawa, Mariame Ali Hassan, Yoshiaki Tabuchi, Ichiro Takasaki, Akihisa Takahashi, Takashi Kondo

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57 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbere29012
JournalPloS one
Volume7
Issue number1
DOIs
Publication statusPublished - 2012 Jan 3

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Furusawa, Y., Fujiwara, Y., Campbell, P., Zhao, Q. L., Ogawa, R., Hassan, M. A., Tabuchi, Y., Takasaki, I., Takahashi, A., & Kondo, T. (2012). DNA double-strand breaks induced by cavitational mechanical effects of ultrasound in cancer cell lines. PloS one, 7(1), [e29012]. https://doi.org/10.1371/journal.pone.0029012