Udroiu Ion, Domenici Fabio, Giliberti Claudia, Bedini Angelico, Palomba Raffaele, Luongo Fabio, Pozzi Deleana, Bordi Federico, Castellano Agostina Congiu
Roma Tre University, Department of Science, Rome, Italy.
Sapienza University, Physics Department, Rome, Italy.
Mutat Res Genet Toxicol Environ Mutagen. 2014 Sep 15;772:20-4. doi: 10.1016/j.mrgentox.2014.07.004. Epub 2014 Jul 25.
Although medical ultrasound offers compelling opportunities to improve therapy in principle, progress in the field has been limited because of an insufficient understanding of the potential genotoxic and cytotoxic effects of ultrasound on biological systems. This paper is mainly focused on an in vitro study of effects with respect to genotoxicity and viability induced by 1- and 3-MHz medical ultrasound in murine fibroblasts (NIH-3T3) at low-intensity exposure (spatial peak temporal average intensity Ita<0.1 W/cm(2)). The NIH-3T3 cells constitute a well-characterized in vitro cell model in which a genotoxic effect can be predicted by means of a reliable and precise murine cytokinesis-block micronucleus assay. A statistically significant increase in the incidence of micronuclei was observed in sonicated 3T3 cells. In particular, the effects were more evident at 1 MHz. Moreover, for each frequency investigated, the occurrence of micronuclei was comparatively more frequent with increasing time of exposure. The possible toxicological implications of the medical ultrasound employed herein deal with the existence of a window of exposure parameters (set well below the intensity of ultrasound cavitation) in which some genotoxic effects may occur without significant cytotoxicity. In this respect, they provide new insight toward the correct risk to benefit balancing of ultrasound-based treatments and for designing innovative therapeutic strategies.
虽然医学超声原则上为改善治疗提供了引人注目的机会，但由于对超声对生物系统潜在的遗传毒性和细胞毒性作用了解不足，该领域的进展一直有限。本文主要聚焦于在低强度暴露（空间峰值时间平均强度Ita<0.1W/cm²）下，1MHz和3MHz医学超声对小鼠成纤维细胞（NIH-3T3）诱导的遗传毒性和活力影响的体外研究。NIH-3T3细胞构成了一个特征明确的体外细胞模型，其中遗传毒性作用可通过可靠且精确的小鼠胞质分裂阻滞微核试验来预测。在超声处理的3T3细胞中观察到微核发生率有统计学意义的增加。特别是，在1MHz时效应更明显。此外，对于所研究的每个频率，随着暴露时间增加，微核的出现相对更频繁。本文所采用的医学超声可能的毒理学意义涉及存在一个暴露参数窗口（设定远低于超声空化强度），在该窗口中可能发生一些遗传毒性作用而无明显细胞毒性。在这方面，它们为基于超声的治疗正确的风险效益平衡以及设计创新治疗策略提供了新的见解。
