Damage in DNA Irradiated with 1.2 MHz Ultrasound and Its Effect on Template Activity of DNA for RNA Synthesis

Kondo, Takashi; Arai, Soichiro; Kuwabara, Mikinori; Yoshii, Giichi; Kano, E.

doi:10.2307/3576590

Cited by 48 publications

(18 citation statements)

References 24 publications

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“…Therefore, it is reasonable to assume that the mechanical effects of US cavitation, such as shear stress, are more essential for DSB formation in cells exposed to US. Consistent with this observation, our classical study in 1985 demonstrated that DSB induction in naked DNA is caused by the mechanical effects of US but not chemical effects [13]. However, from the available literature, there is no direct evidence showing a correlation between such mechanical effects and DSB formation in the cell nucleus.…”

Section: Us-induced Dsb Formation Mechanismsupporting

confidence: 65%

DNA Damage Induced by Ultrasound and Cellular Responses

Furusawa¹,

Kondo²

2017

Mol Biol

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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.

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Section: Us-induced Dsb Formation Mechanismsupporting

confidence: 65%

DNA Damage Induced by Ultrasound and Cellular Responses

Furusawa¹,

Kondo²

2017

Mol Biol

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“…Ultrasonic cavitation can produce many effects on a DNA molecule, including doublestrand breaks, single-strand breaks, rupture of hydrogen bonds, base destruction, and possibly cross-links. 50 These effects may be direct, due to the physical force placed on the molecule, or indirect, secondary to the production of highly reactive sonochemicals such as hydrogen peroxide. 48,50,52 Transfection assays therefore were performed in order to establish that the DNA in a sonicated liposome/DNA complex was still biologically functional.…”

Section: Discussionmentioning

confidence: 99%

“…48,49 Sonication has been demonstrated to cause DNA strand breaks. [50][51][52] We hypothesized that binding of plasmid DNA to cationic liposomes would protect it from damage due to sonication, and we determined that not only complex size but also resistance to DNA damage upon sonication was dependent on lipid composition. The results presented here suggest that DNA can be protected from damage due to ultrasonic cavitation when complexed to cationic liposomes.…”

Section: Discussionmentioning

confidence: 99%

Plasmid DNA is Protected against Ultrasonic Cavitation-Induced Damage when Complexed to Cationic Liposomes

Wasan¹,

Reimer²,

Bally³

1996

Journal of Pharmaceutical Sciences

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Cationic liposomes bound to plasmid DNA are currently used for in vitro and in vivo gene therapy applications, but such complexes readily form large, heterogeneous aggregates that are not appropriate for pharmaceutical development. More importantly, size heterogeneity makes studies focused on optimizing gene transfer to cells difficult to conduct or understand. For this reason we have evaluated the effect of microprobe sonication on these complexes in an effort to achieve process-controlled size homogeneity. Complexes were prepared using a 7.2 kb reporter plasmid and the following liposomal lipid combinations: DDAB/DOPE (50:50 mol %), DDAB/DOPE/PEG-PE (50:45:5 mol %), DDAB/EPC (50:50 mol %), DDAB/EPC/PEG-PE (50:45:5, 50:40:10, 50:35:15 mol %), DODAC/DOPE (50:50 mol %), and DODAC/EPC (50:50 mol %) (DDAB, dimethyldioctadecylammonium bromide; DOPE, dioleoylphosphatidylethanolamine; PEG-PE, monomethoxypolyethylene glycol2000 succinate- distearoylphosphatidylethanolamine; EPC, egg phosphatidylcholine; DODAC, dioleoyldimethylammonium chloride). The influence of complex composition and lipid:DNA ratio was evaluated. Particle size was determined before and after complexation and again after sonication using the quasi-elastic light scattering technique. DNA integrity was assessed via agarose gel electrophoresis. Finally, gene transfection was evaluated using CHO cells that were transfected in vitro with sonicated and unsonicated complexes. It is established in this study that size reduction can occur, but this is dependent on cationic and neutral lipid composition and, in some cases, lipid:DNA ratio. Surprisingly, the process of sonication leaves a significant percentage of the plasmid DNA intact and capable of in vitro transfection. This study shows that plasmid DNA can be protected from damage due to sonication by liposome complex formation. This may indicate that more common pharmaceutical methods for size reduction which subject particles to mechanical stress may be applicable in preparation of liposome/DNA formulations for in vivo application.

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“…Biophysical modes of ultrasonic action can be classified into three main categories; thermal effect, direct effect and cavitation. It is generally accepted that many nonthermal effects of US in biologic systems are attributable to cavitation (Kondo et al 1985). Ultrasonic cavitation of aqueous media, which refers to the formation, growth and collapse of small gas bubbles, occurs over a wide range of frequencies and serves as mediator of any important effects of US (Riesz and Kondo 1992).…”

Section: Introductionmentioning

confidence: 99%