Biologia Molecular: Acesso Aberto

DNA Damage Induced by Ultrasound and Cellular Responses

Abstract

Yukihiro Furusawa and Takashi Kondo

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.