Mechanism of Genome Damage Response Induced by Ultrasoun

• Project/Area Number: 23650304
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Medical systems
• Research Institution: University of Toyama
• Principal Investigator: KONDO Takashi 富山大学, 大学院・医学薬学研究部(医学), 教授 (40143937)
• Co-Investigator(Kenkyū-buntansha): TABUCHI Yoshiaki 富山大学, 生命科学先端研究センター, 准教授 (20322109) ; ZHAO Qing-li 富山大学, 大学院・医学薬学研究部(医学), 助教 (90313593) ; TAKASAKI Ichro 富山大学, 生命科学先端研究センター, 助教 (00397176)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 超音波・DNA損傷 / 二本鎖切断 / リン酸化ヒストンH2AX / キャビテーション / フリーラジカル / DNA-PK / DNA損傷 / ATM / ATR / DNA二本鎖切断

Research Abstract

A likely candidate process has been suggested to involve sonochemical activity, where reactive oxygen species mediate the generation of DNAsingle-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 DNAdouble-strand breaks, 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.

Research Products

• [Journal Article] Regulation of gene expression in human prostate cancer cells with artificially constructed promoters that are activated in response to ultrasound stimulation (2012)
  • Author(s): Ogawa R., A. Morii, A. Watanabe, Z. G. Cui, G. Kagiya, T. Kondo, N. Doi, L. B. Feril
  • Journal Title: Ultrason Sonochem Volume: 20 Issue: 1 Pages: 460-467
  • DOI: 10.1016/j.ultsonch.2012.05.007
  • Peer Reviewed
• [Journal Article] DNA double-strand breaks induced by cavitational mechanical effects of ultrasound in cancer cell lines (2012)
  • Author(s): Furusawa Y., Y. Fujiwara, P. Campbell, Q. L. Zhao, R. Ogawa, M. A. Hassan, Y. Tabuchi, I. Takasaki, A. Takahashi, T. Kondo
  • Journal Title: PLoS ONE Volume: 7 Issue: 1 Pages: e29012-e29012
  • DOI: 10.1371/journal.pone.0029012
  • Peer Reviewed
• [Journal Article] Ultrasound-induced new cellular mechanism involved in drug resistance (2012)
  • Author(s): Hassan MA, Furusawa Y, Minemura M, Rapoport N, Sugiyama T, and Kondo T
  • Journal Title: PLoS One Volume: 7 Issue: 12 Pages: e48291-e48291
  • DOI: 10.1371/journal.pone.0048291
  • Peer Reviewed
• [Journal Article] Inhibition of DNA-dependent protein kinase promotes ultrasound -induced cell death including apoptosis in human leukemia cells (2012)
  • Author(s): Furusawa Y, Fujiwara Y, Hassan MA, Tabuchi Y, Morita A, Enomoto A,and Kondo T
  • Journal Title: Cancer Lett Volume: 322 Issue: 1 Pages: 107-112
  • DOI: 10.1016/j.canlet.2012.02.020
  • Peer Reviewed
• [Journal Article] Ultrasound activates ataxia telangiectasia mutated- and Rad-3 related (ATR)-checkpoint kinase 1 (Chk1) pathway in human leukemia Jurkat cells (2012)
  • Author(s): Furusawa Y, Iizumi T, Fujiwara Y, Hassan MA, Tabuchi Y, Nomura T, and Kondo T
  • Journal Title: Ultrason Sonochem Volume: 19 Issue: 6 Pages: 1246-1251
  • DOI: 10.1016/j.ultsonch.2012.04.003
  • Peer Reviewed
• [Journal Article] Enhanced gene transfection using calcium phosphate co-precipitates and low-intensity pulsed ultrasound (2012)
  • Author(s): Hassan MA, Ahmed IS, Campbell P, Kondo T
  • Journal Title: Eur J Pharmaceut Sci Volume: 47 Pages: 768-773
  • Peer Reviewed
• [Journal Article] Differential cytotoxicity and sonosensitization by sanazole: Effect of cell type and acoustic parameters (2011)
  • Author(s): Hassan MA, Furusawa Y, Zhao Q.L., Takasaki I, Ferl LB Jr., Tachibana K, Minemura M., Sugiyama T, and Kondo T
  • Journal Title: J. Med. Ultrasonics Volume: 38 Issue: 2 Pages: 65-72
  • DOI: 10.1007/s10396-010-0295-2
  • NAID: 10029031195
  • Peer Reviewed
• [Presentation] Roles of intracellular oxidative stress in DNA Damage and apoptosis induced by different physical stressors; ionizing radiation, hyperthermia and ultrasound (2012)
  • Author(s): Kondo T, Hassan MA, Zhao QL, Ogawa R, Tabuchi Y, and Furusawa Y
  • Organizer: 28th RBC-NIRS International Symposium, Radiationassociated Repair Proteins and DNA Repair Network
  • Place of Presentation: Kyoto, Japan.
• [Presentation] Enhancement of ultrasoundor hyperthermia-induced cancer cell killing by antibacterial agents (2012)
  • Author(s): Feril LB, Tachibana K, Kondo T, Ogawa R, Cui ZG
  • Organizer: The 11th International Congress of Hyperthermic Oncology (ICHO) & The 29th Japanese Congress of Thermal Medicine
  • Place of Presentation: Kyoto, Japan
• [Presentation] Enhanced gene transfection using calcium phosphate co-precipitates and low-intesnity pulsed ultrasound (2012)
  • Author(s): Hassan MA, Ahmed IS, Campbell P, Kondo T
  • Organizer: The 39th Annual Meeting and Exposition of the Controolled Release Society
  • Place of Presentation: Quebec, Canada
• [Presentation] Roles of intracellular oxidative stress in DNA Damage and apoptosis induced by different physical stressors; ionizing radiation, hyperthermia and ultrasound (2012)
  • Author(s): Kondo T
  • Organizer: 28th RBC-NIRS International Symposium, Radiation-associated Repair Proteins and DNA Repair Network
  • Place of Presentation: Kyoto
  • Invited
• [Presentation] Roles of intracellular oxidative stress in the enhancement of hyperthermia-induced apoptosis (2012)
  • Author(s): Kondo T
  • Organizer: The 11th International Congress of Hyperthermic Oncology (ICHO) & The 29th Japanese Congress of Thermal Medicine,
  • Place of Presentation: Kyoto
  • Invited
• [Presentation] Enhancement of ultrasound- or hyperthermia-induced cancer cell killing by antibacterial agents (2012)
  • Author(s): Feril LB
  • Organizer: The 11th International Congress of Hyperthermic Oncology (ICHO) & The 29th Japanese Congress of Thermal Medicine
  • Place of Presentation: Kyoto
• [Presentation] Controlling gene expression in human prostate cancer cells by ultrasound-responsive promoters (2012)
  • Author(s): Morii A
  • Organizer: The 11th International Congress of Hyperthermic Oncology (ICHO) & The 29th Japanese Congress of Thermal Medicine
  • Place of Presentation: Kyoto
• [Presentation] Ultrasond induces DNA double strand breaks in genome DNA through the cavitational effects (2011)
  • Author(s): Furusawa Y and Kondo T
  • Organizer: The 20th Annual Meeting of the Japan Society of Sonochemstry and The International Workshop on Advanced Sonochemistry
  • Place of Presentation: Nagoya, Japan
• [Presentation] Gene regulation and sonotransfection by loe-intensity ultrasound resulting in malinant melanoma inhibition (2011)
  • Author(s): Feril LB Jr, Tachibana K, Yamaguchi K, Ikeda-Dantsuji Y, Kondo T, Tabuchi Y, Furusawa Y, and Takasaki I
  • Organizer: The 20th Annual Meeting of the Japan Society of Sonochemstry and The International Workshop on Advanced Sonochemistry
  • Place of Presentation: Nagoya, Japan.
• [Presentation] Mariame MA, Furusawa Y, Minemura M, and Kondo T (2011)
  • Author(s): Mariame MA, Furusawa Y, Minemura M, and Kondo T
  • Organizer: The 20th Annual Meeting of the Japan Society of Sonochemstry and The International Workshop on Advanced Sonochemistry
  • Place of Presentation: Nagoya, Japan.
• [Presentation] Effect of sonication on miRNA expresions and its application for gene expression control with ultrasound (2011)
  • Author(s): Ogawa R, Morii A, Watanabe A, Cui ZG, and Kondo T
  • Organizer: The 20th Annual Meeting of the Japan Society of Sonochemstry and The International Workshop on Advanced Sonochemistry
  • Place of Presentation: Nagoya, Japan.
• [Presentation] In vitro dependence of chemical and biological effects of low intensity pulsed ultrasound on pulse repetition frequency (2011)
  • Author(s): Buldakov MA, Hassan MA, Zhao QL, Cherdyntseva NV, and Kondo T
  • Organizer: The 20th Annual Meeting of the Japan Society of Sonochemstry and The International Workshop on Advanced Sonochemistry
  • Place of Presentation: Nagoya, Japan.
• [Presentation] Ultrasond induces DNA double strand breaks in genome DNA through the cavitational effects. (2011)
  • Author(s): Furusawa Y and Kondo T
  • Organizer: The 20th Annual Meeting of the Japan Society of Sonochemstry and The International Workshop on Advanced Sonochemistry
  • Place of Presentation: Nagoya, Japan
• [Book] 第9章バイオ・医学への応用。音響サイエンスシリーズ,7.音響バブルとソノケミストリー. 日本音響学会編集 (2012)
  • Author(s): 近藤 隆
  • Publisher: コロナ社、東京
• [Book] 音響サイエンスシリーズ,７.音響バブルとソノケミストリー、第９章バイオ・医学への応用 (2012)
  • Author(s): 近藤 隆
  • Publisher: コロナ社
• [Book] Chapter 12: Sonodynamic Therapy in Therapeutic Ultrasound: Mechanisms to Applications (Public Health in the 21st Century), Editor, Frenkel V. (2011)
  • Author(s): Feril LB Jr., Tachibana K, Kondo T, and Campbell P
  • Publisher: Nova Science Publishers, Inc., New York
• [Book] American Institute of Physics, New York (2011)
  • Author(s): Furusawa Y, Fijiwara Y, Zhao Q-L, Hassan MA, Ogawa R, Tabuchi Y, Takasaki I,Takahashi A, Ohnishi T, and Kondo T
  • Publisher: Ultrasound-induced DNA damage and signal transductions indicated by gamma H2AX. 10th International Symposium on Therapeutic Ultrasound (ISTU2010) Editors, Matsumoto Y, Crum LA, and ter Haar GR
• [Book] AIP Conf Proc 1359, American Institute of Physics, (2011)
  • Author(s): Furusawa Y, Fujiwara Y, Zhao Q-L, Hassan MA, Ogawa R, Tabuchi Y, Takasaki I,Takahashi A, Ohnishi T, and Kondo T
  • Total Pages: 4
  • Publisher: 10th International Symposium on Therapeutic Ultrasound (ISTU2010)
• [Remarks]
  • URL: http://www.med.u-toyama.ac.jp/radsci/index.html