DNA Damage Induced by Ultrasound and Cellular Responses

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 tumors. Ultrasound (US) causes multiple thermal and non-thermal effects, such as mechanical and chemical stresses, that can result in damage to the cellular membrane and nucleus, leading to transient membrane pores, alterations in gene expression, and cell death, including apoptosis. On the basis of its biological effects US has been proposed as a new drug delivery and molecular targeting tool for cancer therapy. However, the molecular mechanisms involved in USinduced cell killing are not yet fully understood. Recently, we have reported that the mechanical effects of US elicit DNA single strand as well as double strand breaking-the most cytotoxic form of DNA damage, which initiates subsequent DNA damage response associated with DNA repair, cell cycle arrest, and cell death. Here in the present study we have focused on one of the most significant biological effects of US, i.e., DNA damage and discussed the underlying mechanisms and a unique cellular response. In addition, we have described the characteristic DNA damage response induced by heat stress, which could have caused by the thermal effects of US. Moreover, the study will enrich the literature relevant to furthering our understanding of US for future applications in cancer therapy.

Zinc Oxide Nanocrystals and High-Energy Shock Waves: A New Synergy for the Treatment of Cancer Cells

“…Based on these results and the state of the art, it is thus hypothesized here that the apoptosis is caused by cell mechanical injury upon ZnO NCs and SW co-administration. Actually, it was previously observed that mechanical stress could result in DNA damage, with the activation of the apoptotic pathway (Furusawa and Kondo, 2017). Moreover, it was reported that SW mechanotransduction could exert an apoptotic pathway (d 'Agostino et al, 2015), and the previously cited "nanoscalpel effect" is also related to apoptosis (Osminkina et al, 2015).…”

Synthesis of echogenic liposomes for sonoporation

“…Furusawa et al. have reported that damage on genetic materials can be induced low intensity ultrasound whose intensity is 0.3 W/cm 2 [68–70]. As can be observed in Figure 6, sonication of 1 W/cm 2 on pure siRNA reduced the measured amount of siRNA approximately 15%.…”

Landscape of Cellular Bioeffects Triggered by Ultrasound-Induced Sonoporation

“…On the other hand, DNA-PK is responsible for Akt phosphorylation and DNA-PK inhibitor-suppressed sonoporation-mediated death in p53+ and p53-. Based on these findings, the authors claimed that DNA-PK might be an interesting target for US-targeted anticancer therapy [ 214 ]. In agreement with all the presented results, DNA replication was found to be significantly lengthened even up to 250% in US-exposed cells proving serious DNA damage [ 141 ].…”

“…The role of Chk2 in post-US cell cycle regulation remains unclear. Since ATR and ATM preferentially activate Chk1 and Chk2, respectively [ 221 ] and because ATM and Chk2 can activate p53, the role of the ATM-Chk2 axis in p53-induced apoptosis and cell cycle arrest should be addressed in future research [ 214 ]. Heat stress can induce cell cycle arrest by p21 upregulation in G1 phase and by the ATK-Chk1-CDC25A pathway in G2/M phase; however, these phenomena have not yet been proven in sonoporated cells [ 214 ].…”