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
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U2 - 10.1063/1.3607926
DO - 10.1063/1.3607926
M3 - Conference contribution
AN - SCOPUS:80053627872
SN - 9780735409170
T3 - AIP Conference Proceedings
SP - 322
EP - 325
BT - 10th International Symposium on Therapeutic Ultrasound, ISTU 2010
T2 - 10th International Symposium on Therapeutic Ultrasound, ISTU 2010
Y2 - 9 June 2010 through 12 June 2010
ER -