The High-Throughput In Vitro CometChip Assay for the Analysis of Metal Oxide Nanomaterial Induced DNA Damage

Overview

Journal Nanomaterials (Basel)

Date 2022 Jun 10

PMID 35683698

Authors

Andrey Boyadzhiev

Silvia Aidee Solorio-Rodriguez

Dongmei Wu

Mary-Luyza Avramescu

Pat Rasmussen

Sabina Halappanavar

Affiliations

Soon will be listed here.

Abstract

Metal oxide nanomaterials (MONMs) are among the most highly utilized classes of nanomaterials worldwide, though their potential to induce DNA damage in living organisms is known. High-throughput in vitro assays have the potential to greatly expedite analysis and understanding of MONM induced toxicity while minimizing the overall use of animals. In this study, the high-throughput CometChip assay was used to assess the in vitro genotoxic potential of pristine copper oxide (CuO), zinc oxide (ZnO), and titanium dioxide (TiO) MONMs and microparticles (MPs), as well as five coated/surface-modified TiO NPs and zinc (II) chloride (ZnCl) and copper (II) chloride (CuCl) after 2-4 h of exposure. The CuO NPs, ZnO NPs and MPs, and ZnCl exposures induced dose- and time-dependent increases in DNA damage at both timepoints. TiO NPs surface coated with silica or silica-alumina and one pristine TiO NP of rutile crystal structure also induced subtle dose-dependent DNA damage. Concentration modelling at both post-exposure timepoints highlighted the contribution of the dissolved species to the response of ZnO, and the role of the nanoparticle fraction for CuO mediated genotoxicity, showing the differential impact that particle and dissolved fractions can have on genotoxicity induced by MONMs. The results imply that solubility alone may be insufficient to explain the biological behaviour of MONMs.

Citing Articles

Mechanisms and Assessment of Genotoxicity of Metallic Engineered Nanomaterials in the Human Environment.

Liu B, Wallace Hayes A Biomedicines. 2024; 12(10).

PMID: 39457713 PMC: 11504605. DOI: 10.3390/biomedicines12102401.

A Systematic Genotoxicity Assessment of a Suite of Metal Oxide Nanoparticles Reveals Their DNA Damaging and Clastogenic Potential.

Solorio-Rodriguez S, Wu D, Boyadzhiev A, Christ C, Williams A, Halappanavar S Nanomaterials (Basel). 2024; 14(9).

PMID: 38727337 PMC: 11085103. DOI: 10.3390/nano14090743.

The utilization of nanotechnology in the female reproductive system and related disorders.

Luo X, Jia K, Xing J, Yi J Heliyon. 2024; 10(3):e25477.

PMID: 38333849 PMC: 10850912. DOI: 10.1016/j.heliyon.2024.e25477.

Toxicity of Metal Oxide Nanoparticles: Looking through the Lens of Toxicogenomics.

Boyadzhiev A, Wu D, Avramescu M, Williams A, Rasmussen P, Halappanavar S Int J Mol Sci. 2024; 25(1).

PMID: 38203705 PMC: 10779048. DOI: 10.3390/ijms25010529.

Editorial for the Special Issue "Biological and Toxicological Studies of Nanoparticles".

Joubert O Nanomaterials (Basel). 2023; 13(13).

PMID: 37446483 PMC: 10343638. DOI: 10.3390/nano13131968.

References

Moschini E, Gualtieri M, Colombo M, Fascio U, Camatini M, Mantecca P . The modality of cell-particle interactions drives the toxicity of nanosized CuO and TiO₂ in human alveolar epithelial cells. Toxicol Lett. 2013; 222(2):102-16. DOI: 10.1016/j.toxlet.2013.07.019. View

Di Virgilio A, Reigosa M, Arnal P, Fernandez Lorenzo de Mele M . Comparative study of the cytotoxic and genotoxic effects of titanium oxide and aluminium oxide nanoparticles in Chinese hamster ovary (CHO-K1) cells. J Hazard Mater. 2010; 177(1-3):711-8. DOI: 10.1016/j.jhazmat.2009.12.089. View

Seo J, Tryndyak V, Wu Q, Dreval K, Pogribny I, Bryant M . Quantitative comparison of in vitro genotoxicity between metabolically competent HepaRG cells and HepG2 cells using the high-throughput high-content CometChip assay. Arch Toxicol. 2019; 93(5):1433-1448. DOI: 10.1007/s00204-019-02406-9. View

Magaye R, Zhao J, Bowman L, Ding M . Genotoxicity and carcinogenicity of cobalt-, nickel- and copper-based nanoparticles. Exp Ther Med. 2012; 4(4):551-561. PMC: 3501377. DOI: 10.3892/etm.2012.656. View

Fresegna A, Ursini C, Ciervo A, Maiello R, Casciardi S, Iavicoli S . Assessment of the Influence of Crystalline Form on Cyto-Genotoxic and Inflammatory Effects Induced by TiO Nanoparticles on Human Bronchial and Alveolar Cells. Nanomaterials (Basel). 2021; 11(1). PMC: 7835860. DOI: 10.3390/nano11010253. View

El Yamani N, Collins A, Runden-Pran E, Fjellsbo L, Shaposhnikov S, Zienolddiny S . In vitro genotoxicity testing of four reference metal nanomaterials, titanium dioxide, zinc oxide, cerium oxide and silver: towards reliable hazard assessment. Mutagenesis. 2016; 32(1):117-126. DOI: 10.1093/mutage/gew060. View

Semisch A, Ohle J, Witt B, Hartwig A . Cytotoxicity and genotoxicity of nano - and microparticulate copper oxide: role of solubility and intracellular bioavailability. Part Fibre Toxicol. 2014; 11:10. PMC: 3943586. DOI: 10.1186/1743-8977-11-10. View

Elespuru R, Pfuhler S, Aardema M, Chen T, Doak S, Doherty A . Genotoxicity Assessment of Nanomaterials: Recommendations on Best Practices, Assays, and Methods. Toxicol Sci. 2018; 164(2):391-416. DOI: 10.1093/toxsci/kfy100. View

Siivola K, Suhonen S, Hartikainen M, Catalan J, Norppa H . Genotoxicity and cellular uptake of nanosized and fine copper oxide particles in human bronchial epithelial cells in vitro. Mutat Res Genet Toxicol Environ Mutagen. 2020; 856-857:503217. DOI: 10.1016/j.mrgentox.2020.503217. View

10.

Huang Y, Cambre M, Lee H . The Toxicity of Nanoparticles Depends on Multiple Molecular and Physicochemical Mechanisms. Int J Mol Sci. 2017; 18(12). PMC: 5751303. DOI: 10.3390/ijms18122702. View

11.

Sykora P, Chiari Y, Heaton A, Moreno N, Glaberman S, Sobol R . Application of the CometChip platform to assess DNA damage in field-collected blood samples from turtles. Environ Mol Mutagen. 2018; 59(4):322-333. PMC: 5902651. DOI: 10.1002/em.22183. View

12.

Martell J, Guidotti T . Trading One Risk for Another: Consequences of the Unauthenticated Treatment and Prevention of Silicosis in Ontario Miners in the McIntyre Powder Aluminum Inhalation Program. New Solut. 2021; 31(4):422-433. PMC: 8739567. DOI: 10.1177/10482911211037007. View

13.

Heim J, Felder E, Tahir M, Kaltbeitzel A, Heinrich U, Brochhausen C . Genotoxic effects of zinc oxide nanoparticles. Nanoscale. 2015; 7(19):8931-8. DOI: 10.1039/c5nr01167a. View

14.

Rahman L, Wu D, Johnston M, William A, Halappanavar S . Toxicogenomics analysis of mouse lung responses following exposure to titanium dioxide nanomaterials reveal their disease potential at high doses. Mutagenesis. 2016; 32(1):59-76. PMC: 5180171. DOI: 10.1093/mutage/gew048. View

15.

Oliver L, Sampara P, Pearson D, Martell J, Zarnke A . Sarcoidosis in Northern Ontario hard-rock miners: A case series. Am J Ind Med. 2022; 65(4):268-280. PMC: 10138725. DOI: 10.1002/ajim.23333. View

16.

Ivask A, Titma T, Visnapuu M, Vija H, Kakinen A, Sihtmae M . Toxicity of 11 Metal Oxide Nanoparticles to Three Mammalian Cell Types In Vitro. Curr Top Med Chem. 2015; 15(18):1914-29. DOI: 10.2174/1568026615666150506150109. View

17.

Bengtson S, Kling K, Madsen A, Noergaard A, Jacobsen N, Clausen P . No cytotoxicity or genotoxicity of graphene and graphene oxide in murine lung epithelial FE1 cells in vitro. Environ Mol Mutagen. 2016; 57(6):469-82. PMC: 5084775. DOI: 10.1002/em.22017. View

18.

Arlt V, Gingerich J, Schmeiser H, Phillips D, Douglas G, White P . Genotoxicity of 3-nitrobenzanthrone and 3-aminobenzanthrone in MutaMouse and lung epithelial cells derived from MutaMouse. Mutagenesis. 2008; 23(6):483-90. DOI: 10.1093/mutage/gen037. View

19.

Graczyk H, Lewinski N, Zhao J, Concha-Lozano N, Riediker M . Characterization of Tungsten Inert Gas (TIG) Welding Fume Generated by Apprentice Welders. Ann Occup Hyg. 2015; 60(2):205-19. PMC: 4738234. DOI: 10.1093/annhyg/mev074. View

20.

Pavan C, Delle Piane M, Gullo M, Filippi F, Fubini B, Hoet P . The puzzling issue of silica toxicity: are silanols bridging the gaps between surface states and pathogenicity?. Part Fibre Toxicol. 2019; 16(1):32. PMC: 6697921. DOI: 10.1186/s12989-019-0315-3. View