Potential genotoxic effects of low-intensity ultrasound on fibroblasts, evaluated with the cytokinesis-block micronucleus assay

Udroiu, Ion; Domenici, Fabio; Giliberti, Claudia; Bedini, Angelico; Palomba, Raffaele; Luongo, Fabio; Pozzi, Deleana; Bordi, F.; Castellano, A. Congiu

doi:10.1016/j.mrgentox.2014.07.004

Cited by 9 publications

(19 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The presence of this clastogenic damage was confirmed also by H2AX phosphorylation. This is in accordance with other works that found that 1 MHz sonication causes DNA breakage as evidenced by Comet assay [Milowska and Gabryelak, ; Furusawa et al, ], Micronucleus test [Udroiu et al, ] and H2AX phosphorylation [Furusawa et al, ; Buldakov et al, ]. On the other hand, our results in a preliminary experiment (data not shown) with lower intensities (70 and 140 mW/cm 2 ) did not show any increase of MN frequencies, even with long exposures (30 min).…”

Section: Discussionsupporting

confidence: 93%

See 1 more Smart Citation

Genomic damage induced by 1‐MHz ultrasound in vitro

Udroiu

Marinaccio

Bedini

et al. 2017

Environ and Mol Mutagen

Self Cite

View full text Add to dashboard Cite

Genotoxic effects of therapeutic ultrasound are poorly documented, when compared with the wide use of this physical agent. The aim of this work was to investigate the clastogenic and aneugenic potential of 1 MHz ultrasound, employing intensities (200 and 300 mW/cm 2 ) above the cavitational threshold, but in the range of those normally used in therapeutics. Both normal fibroblasts (AG01522) and tumoral cells (MCF-7) were sonicated. While no effects on viability were noted, significant increases of CREST-negative micronuclei (indicative of clastogenesis) and CREST-positive micronuclei (indicative of aneuploidy) were detected. Clastogenesis was confirmed by increases of g-H2AX foci, while increases of spindle anomalies confirmed the induction of aneuploidy. Our results confirm previous works that showed ultrasoundinduced DNA breakage. Moreover, our experiments show that the known effect of ultrasoundinduced damage to microtubules is also able to damage the mitotic spindle and induce aneuploidy. On the overall, this work highlights the importance to further investigate the potential risks related to therapeutics US. Environ. Mol. Mutagen. 59:60-68, 2018.V C 2017 Wiley Periodicals, Inc.

show abstract

Section: Discussionsupporting

confidence: 93%

“…Early studies in the 1970s gave conflicting results [Martin, ], and this may be due to the fact that in those years control of exposure conditions was quite inadequate. On the other hand, some recent works evidenced DNA breakage after sonication of cells [Milowska and Gabryelak, ; Furusawa et al, ; Udroiu et al, ; Buldakov et al, ].…”

Section: Introductionmentioning

confidence: 99%

Genomic damage induced by 1‐MHz ultrasound in vitro

Udroiu

Marinaccio

Bedini

et al. 2017

Environ and Mol Mutagen

Self Cite

View full text Add to dashboard Cite

show abstract

“…With a half‐value depth of 4 cm for 1‐MHz ultrasound, this means that thousands of patients have their tissues sonicated with more than 500 mW/cm 2 , a value five times above the cavitation threshold. Genotoxic effects (among other ones) of cavitational ultrasound have been demonstrated by several authors (Milowska and Gabryelak ; Furusawa et al ; Udroiu et al ; Buldakov et al ; Udroiu et al ) and are mechanistically justified by sonolysis‐induced ROS production and consequent DNA breakage (Milowska and Gabryelak ; Furusawa et al ). Nonetheless, the present work evidenced another mechanism of action that can affect the genome (spindle disturbance) and that seem to be present even at low, noncavitational intensities.…”

Section: Discussionmentioning

confidence: 97%

“…We employed intensities below (70 mW/cm 2 ), around (140 mW/cm 2 ), and above (300 mW/cm 2 ) the cavitation threshold. A clastogenic effect (DNA breakage), due to ROS formation, of ultrasonic cavitation have been demonstrated with different techniques such as Comet assay (Furusawa et al ), H2AX phosphorylation (Furusawa et al ; Udroiu et al ), and Micronucleus test (Udroiu et al ; Udroiu et al ). On the other hand, it has also been demonstrated that DNA breakage is not induced below the cavitation threshold (Pozzi et al ; Furusawa et al ).…”

Section: Discussionmentioning

confidence: 99%

In vitro effects of 1‐MHz ultrasound on the mitotic spindle

Udroiu

Coluzzi

Bedini

et al. 2019

Environ and Mol Mutagen

Self Cite

View full text Add to dashboard Cite

The effects of ultrasound on the cytoskeleton, comprising microtubules, had been studied decades ago. Nonetheless, very little attention has been paid to the effects of ultrasound on the mitotic spindle, which is also formed by microtubules. In this study, we treated human fibroblasts and human cancer cells (HeLa and MCF‐7) with 1‐MHz ultrasound at low intensities (70, 140, and 300 mW/cm2). In all cell lines, 5 min after the end of sonication, we found an intensity‐dependent increase of mitotic abnormalities (including multipolar spindles). Two hours after sonication, these abnormalities were present, but at much lower frequencies. Twenty‐four hours after sonication, mitotic abnormalities were at the same level of untreated samples, suggesting a transient effect due to ultrasound. Beside abnormalities of the mitotic spindle, we also observed an increase of metaphases with nonaligned chromosomes. The mitotic index of fibroblasts and HeLa cells, two hours after sonication, showed an intensity‐dependent decrease; this was not observed in MCF‐7 cells. In agreement with this last result, ultrasound‐induced growth inhibition (which was also intensity‐dependent) was more marked in fibroblasts and HeLa cells compared to MCF‐7 cells. This work indicates that therapeutic ultrasound, even at intensities below the cavitation threshold, can affect genome integrity, showing the need to increase the knowledge of the potential risks of ultrasound to human health. Environ. Mol. Mutagen. 2019. © 2019 Wiley Periodicals, Inc.

show abstract

“…Micronuclei are produced under hypotonic condi tions [11] and upon ultrasonication in vitro and in vivo [37,38].…”

Section: Influences Leading To Formation Of Micronucleimentioning

confidence: 99%

Biogenesis of micronuclei

Kisurina-Evgenieva

Sutiagina

Онищенко

2016

Biochemistry Moscow

View full text Add to dashboard Cite

The presence of micronuclei in a cell is an indicator of DNA damage and genetic instability. In this review, mechanisms of emergence of micronuclei, their functional activity, and pathways of elimination are discussed. It is supposed that morphological and functional varieties of micronuclei as well as their degradation pathways can be determined by the chromosomal material localized inside these cell structures.

show abstract

Potential genotoxic effects of low-intensity ultrasound on fibroblasts, evaluated with the cytokinesis-block micronucleus assay

Cited by 9 publications

References 43 publications

Genomic damage induced by 1‐MHz ultrasound in vitro

Genomic damage induced by 1‐MHz ultrasound in vitro

In vitro effects of 1‐MHz ultrasound on the mitotic spindle

Biogenesis of micronuclei

Contact Info

Product

Resources

About