Abstract
Ultrasound (US) has been shown to induce cancer cell death via different forms including apoptosis. Here, we report the potential of low-intensity pulsed US (LIPUS) to induce genomic DNA damage and subsequent DNA damage response. Using the ionizing radiation-induced DNA doublestrand breaks (DSBs) as the positive control, we were able to observe the induction of DSBs (as neutral comet tails) and the subsequent formation of gammaH2AX-positive foci (by immunofluorescence detection) in human leukemia cells following exposure to LIPUS. The LIPUS-induced DNA damage arose most likely from the mechanical, but not sonochemical, effect of cavitation, based on our observation that the suppression of inertial cavitation abrogated the gammH2AX foci formation, whereas scavenging of free radical formation (e.g., hydroxyl radical) had no protective effect on it. Treatment with the specific kinase inhibitor of ATM or DNA-PKcs, which can phosphorylate H2AX Ser139, revealed that US-induced gammaH2AX was inhibited more effectively by the DNA-PK inhibitor than ATM kinase inhibitor. Notably, these inhibitor effects were opposite to those with radiation-induced gammH2AX. In conclusion, we report, for the first time that US can induce DNA damage and the DNA damage response as indicated by gammaH2AX was triggered by the cavitational mechanical effects. Thus, it is expected that the data shown here may provide a better understanding of the cellular responses to US.
| Original language | English |
|---|---|
| Title of host publication | AIP Conference Proceedings |
| Pages | 322-325 |
| Number of pages | 4 |
| Volume | 1359 |
| DOIs | |
| Publication status | Published - 2011 |
| Event | 10th International Symposium on Therapeutic Ultrasound, ISTU 2010 - Tokyo, Japan Duration: 2010 Jun 9 → 2010 Jun 12 |
Other
| Other | 10th International Symposium on Therapeutic Ultrasound, ISTU 2010 |
|---|---|
| Country | Japan |
| City | Tokyo |
| Period | 10/6/9 → 10/6/12 |
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Keywords
- Cavitation
- DNA damage
- GammaH2AX
- Ultrasound
ASJC Scopus subject areas
- Physics and Astronomy(all)
Cite this
Ultrasound-induced DNA damage and signal transductions indicated by gammaH2AX. / Furusawa, Yukihiro; Fujiwara, Yoshisada; Zhao, Qing Li; Hassan, Mariame Ali; Ogawa, Ryohei; Tabuchi, Yoshiaki; Takasaki, Ichiro; Takahashi, Akihisa; Ohnishi, Takeo; Kondo, Takashi.
AIP Conference Proceedings. Vol. 1359 2011. p. 322-325.Research output: Chapter in Book/Report/Conference proceeding › Conference contribution
}
TY - GEN
T1 - Ultrasound-induced DNA damage and signal transductions indicated by gammaH2AX
AU - Furusawa, Yukihiro
AU - Fujiwara, Yoshisada
AU - Zhao, Qing Li
AU - Hassan, Mariame Ali
AU - Ogawa, Ryohei
AU - Tabuchi, Yoshiaki
AU - Takasaki, Ichiro
AU - Takahashi, Akihisa
AU - Ohnishi, Takeo
AU - Kondo, Takashi
PY - 2011
Y1 - 2011
N2 - Ultrasound (US) has been shown to induce cancer cell death via different forms including apoptosis. Here, we report the potential of low-intensity pulsed US (LIPUS) to induce genomic DNA damage and subsequent DNA damage response. Using the ionizing radiation-induced DNA doublestrand breaks (DSBs) as the positive control, we were able to observe the induction of DSBs (as neutral comet tails) and the subsequent formation of gammaH2AX-positive foci (by immunofluorescence detection) in human leukemia cells following exposure to LIPUS. The LIPUS-induced DNA damage arose most likely from the mechanical, but not sonochemical, effect of cavitation, based on our observation that the suppression of inertial cavitation abrogated the gammH2AX foci formation, whereas scavenging of free radical formation (e.g., hydroxyl radical) had no protective effect on it. Treatment with the specific kinase inhibitor of ATM or DNA-PKcs, which can phosphorylate H2AX Ser139, revealed that US-induced gammaH2AX was inhibited more effectively by the DNA-PK inhibitor than ATM kinase inhibitor. Notably, these inhibitor effects were opposite to those with radiation-induced gammH2AX. In conclusion, we report, for the first time that US can induce DNA damage and the DNA damage response as indicated by gammaH2AX was triggered by the cavitational mechanical effects. Thus, it is expected that the data shown here may provide a better understanding of the cellular responses to US.
AB - Ultrasound (US) has been shown to induce cancer cell death via different forms including apoptosis. Here, we report the potential of low-intensity pulsed US (LIPUS) to induce genomic DNA damage and subsequent DNA damage response. Using the ionizing radiation-induced DNA doublestrand breaks (DSBs) as the positive control, we were able to observe the induction of DSBs (as neutral comet tails) and the subsequent formation of gammaH2AX-positive foci (by immunofluorescence detection) in human leukemia cells following exposure to LIPUS. The LIPUS-induced DNA damage arose most likely from the mechanical, but not sonochemical, effect of cavitation, based on our observation that the suppression of inertial cavitation abrogated the gammH2AX foci formation, whereas scavenging of free radical formation (e.g., hydroxyl radical) had no protective effect on it. Treatment with the specific kinase inhibitor of ATM or DNA-PKcs, which can phosphorylate H2AX Ser139, revealed that US-induced gammaH2AX was inhibited more effectively by the DNA-PK inhibitor than ATM kinase inhibitor. Notably, these inhibitor effects were opposite to those with radiation-induced gammH2AX. In conclusion, we report, for the first time that US can induce DNA damage and the DNA damage response as indicated by gammaH2AX was triggered by the cavitational mechanical effects. Thus, it is expected that the data shown here may provide a better understanding of the cellular responses to US.
KW - Cavitation
KW - DNA damage
KW - GammaH2AX
KW - Ultrasound
UR - http://www.scopus.com/inward/record.url?scp=80053627872&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=80053627872&partnerID=8YFLogxK
U2 - 10.1063/1.3607926
DO - 10.1063/1.3607926
M3 - Conference contribution
AN - SCOPUS:80053627872
SN - 9780735409170
VL - 1359
SP - 322
EP - 325
BT - AIP Conference Proceedings
ER -