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Research Articles

Multiparametric in vitro genotoxicity assessment of different variants of amorphous silica nanomaterials in rat alveolar epithelial cells

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Pages 511-528 | Received 01 Mar 2023, Accepted 20 Sep 2023, Published online: 19 Oct 2023

References

  • Ajdary, M., M. A. Moosavi, M. Rahmati, M. Falahati, M. Mahboubi, A. Mandegary, S. Jangjoo, R. Mohammadinejad, and R. S. Varma. 2018. “Health Concerns of Various Nanoparticles: A Review of Their in Vitro and in Vivo Toxicity.” Nanomaterials (Basel, Switzerland) 8 (9): 8. https://doi.org/10.3390/nano8090634
  • Arts, J. H., H. Muijser, E. Duistermaat, K. Junker, and C. F. Kuper. 2007. “Five-Day Inhalation Toxicity Study of Three Types of Synthetic Amorphous Silicas in Wistar Rats and Post-Exposure Evaluations for up to 3 Months.” Food and Chemical Toxicology 45 (10): 1856–1867. https://doi.org/10.1016/j.fct.2007.04.001
  • Azqueta, A., and A. R. Collins. 2013. “The Essential Comet Assay: A Comprehensive Guide to Measuring DNA Damage and Repair.” Archives of Toxicology 87 (6): 949–968. https://doi.org/10.1007/s00204-013-1070-0
  • Azqueta, A., and M. Dusinska. 2015. “The Use of the Comet Assay for the Evaluation of the Genotoxicity of Nanomaterials.” Frontiers in Genetics 6: 239. https://doi.org/10.3389/fgene.2015.00239
  • Azqueta, A., H. Stopper, B. Zegura, M. Dusinska, and P. Moller. 2022. “Do Cytotoxicity and Cell Death Cause False Positive Results in the in Vitro Comet Assay?” Mutation Research. Genetic Toxicology and Environmental Mutagenesis 881: 503520. https://doi.org/10.1016/j.mrgentox.2022.503520
  • Bahl, A., B. Hellack, M. Balas, A. Dinischiotu, M. Wiemann, J. Brinkmann, A. Luch, B. Y. Renard, and A. Haase. 2019. “Recursive Feature Elimination in Random Forest Classification Supports Nanomaterial Grouping.” NanoImpact 15: 100179. https://doi.org/10.1016/j.impact.2019.100179
  • Bessa, M. J., C. Costa, J. Reinosa, C. Pereira, S. Fraga, J. Fernandez, M. A. Banares, and J. P. Teixeira. 2017. “Moving into Advanced Nanomaterials. Toxicity of Rutile TiO2 Nanoparticles Immobilized in Nanokaolin Nanocomposites on HepG2 Cell Line.” Toxicology and Applied Pharmacology 316: 114–122. https://doi.org/10.1016/j.taap.2016.12.018
  • Brandão, F., C. Costa, M. J. Bessa, E. Dumortier, F. Debacq-Chainiaux, R. Hubaux, M. Salmon, et al. 2021. “Genotoxicity and Gene Expression in the Rat Lung Tissue following Instillation and Inhalation of Different Variants of Amorphous Silica Nanomaterials (aSiO2 NM).” Nanomaterials (Basel, Switzerland) 11 (6): 11. https://doi.org/10.3390/nano11061502
  • Chen, Z., Y. Wang, T. Ba, Y. Li, J. Pu, T. Chen, Y. Song, et al. 2014. “Genotoxic Evaluation of Titanium Dioxide Nanoparticles in Vivo and in Vitro.” Toxicology Letters 226 (3): 314–319. https://doi.org/10.1016/j.toxlet.2014.02.020
  • Clift, M. J. D., G. J. S. Jenkins, and S. H. Doak. 2020. “An Alternative Perspective towards Reducing the Risk of Engineered Nanomaterials to Human Health.” Small (Weinheim an Der Bergstrasse, Germany) 16 (36): e2002002. https://doi.org/10.1002/smll.202002002
  • Croissant, J. G., K. S. Butler, J. I. Zink, and C. J. Brinker. 2020. “Synthetic Amorphous Silica Nanoparticles: toxicity, Biomedical and Environmental Implications.” Nature Reviews Materials 5 (12): 886–909. https://doi.org/10.1038/s41578-020-0230-0
  • Decan, N., D. Wu, A. Williams, S. Bernatchez, M. Johnston, M. Hill, and S. Halappanavar. 2016. “Characterization of in Vitro Genotoxic, Cytotoxic and Transcriptomic Responses following Exposures to Amorphous Silica of Different Sizes.” Mutation Research. Genetic Toxicology and Environmental Mutagenesis 796: 8–22. https://doi.org/10.1016/j.mrgentox.2015.11.011
  • Di Cristo, L., D. Movia, M. G. Bianchi, M. Allegri, B. M. Mohamed, A. P. Bell, C. Moore, et al. 2016. “Proinflammatory Effects of Pyrogenic and Precipitated Amorphous Silica Nanoparticles in Innate Immunity Cells.” Toxicological Sciences: An Official Journal of the Society of Toxicology 150 (1): 40–53. https://doi.org/10.1093/toxsci/kfv258
  • Doak, S. H., and M. Dusinska. 2017. “NanoGenotoxicology: Present and the Future.” Mutagenesis 32 (1): 1–4. https://doi.org/10.1093/mutage/gew066
  • Duan, J., Y. Yu, Y. Li, Y. Yu, Y. Li, X. Zhou, P. Huang, and Z. Sun. 2013. “Toxic Effect of Silica Nanoparticles on Endothelial Cells through DNA Damage Response via Chk1-Dependent G2/M Checkpoint.” PLoS One 8 (4): e62087. https://doi.org/10.1371/journal.pone.0062087
  • Dusinska, M., E. Mariussen, E. Rundén-Pran, A. M. Hudecova, E. Elje, A. Kazimirova, N. El Yamani, N. Dommershausen, J. Tharmann, and D. Fieblinger. 2019. “In Vitro Approaches for Assessing the Genotoxicity of Nanomaterials.” Nanotoxicity, 83–122. Berlin, Germany: Springer.
  • El Yamani, N., A. R. Collins, E. Runden-Pran, L. M. Fjellsbo, S. Shaposhnikov, S. Zienolddiny, and M. Dusinska. 2017. “In Vitro Genotoxicity Testing of Four Reference Metal Nanomaterials, Titanium Dioxide, Zinc Oxide, Cerium Oxide and Silver: Towards Reliable Hazard Assessment.” Mutagenesis 32 (1): 117–126. https://doi.org/10.1093/mutage/gew060
  • Gao, F., N. Ma, H. Zhou, Q. Wang, H. Zhang, P. Wang, H. Hou, H. Wen, and L. Li. 2016. “Zinc Oxide Nanoparticles-Induced Epigenetic Change and G2/M Arrest Are Associated with Apoptosis in Human Epidermal Keratinocytes.” International Journal of Nanomedicine 11: 3859–3874. https://doi.org/10.2147/IJN.S107021
  • Gonzalez, L., M. Lukamowicz-Rajska, L. C. Thomassen, C. E. Kirschhock, L. Leyns, D. Lison, J. A. Martens, A. Elhajouji, and M. Kirsch-Volders. 2014. “Co-Assessment of Cell Cycle and Micronucleus Frequencies Demonstrates the Influence of Serum on the in Vitro Genotoxic Response to Amorphous Monodisperse Silica Nanoparticles of Varying Sizes.” Nanotoxicology 8 (8): 876–884. https://doi.org/10.3109/17435390.2013.842266
  • Gonzalez, L., L. C. Thomassen, G. Plas, V. Rabolli, D. Napierska, I. Decordier, M. Roelants, et al. 2010. “Exploring the Aneugenic and Clastogenic Potential in the Nanosize Range: A549 Human Lung Carcinoma Cells and Amorphous Monodisperse Silica Nanoparticles as Models.” Nanotoxicology 4 (4): 382–395. https://doi.org/10.3109/17435390.2010.501913
  • Großgarten, M., M. Holzlechner, A. Vennemann, A. Balbekova, K. Wieland, M. Sperling, B. Lendl, M. Marchetti-Deschmann, U. Karst, and M. Wiemann. 2018. “Phosphonate Coating of SiO2 Nanoparticles Abrogates Inflammatory Effects and Local Changes of the Lipid Composition in the Rat Lung: A Complementary Bioimaging Study.” Particle and Fibre Toxicology 15 (1): 31. https://doi.org/10.1186/s12989-018-0267-z
  • Guadagnini, R., B. Halamoda Kenzaoui, L. Walker, G. Pojana, Z. Magdolenova, D. Bilanicova, M. Saunders, et al. 2015. “Toxicity Screenings of Nanomaterials: challenges Due to Interference with Assay Processes and Components of Classic in Vitro Tests.” Nanotoxicology 9 (1): 13–24. https://doi.org/10.3109/17435390.2013.829590
  • Guichard, Y., C. Fontana, E. Chavinier, F. Terzetti, L. Gate, S. Binet, and C. Darne. 2016. “Cytotoxic and Genotoxic Evaluation of Different Synthetic Amorphous Silica Nanomaterials in the V79 Cell Line.” Toxicology and Industrial Health 32 (9): 1639–1650. https://doi.org/10.1177/0748233715572562
  • Guidi, P., M. Nigro, M. Bernardeschi, P. Lucchesi, V. Scarcelli, and G. Frenzilli. 2015. “Does the Crystal Habit Modulate the Genotoxic Potential of Silica Particles? A Cytogenetic Evaluation in Human and Murine Cell Lines.” Mutation Research. Genetic Toxicology and Environmental Mutagenesis 792: 46–52. https://doi.org/10.1016/j.mrgentox.2015.07.005
  • Gurcan, C., H. Taheri, A. Bianco, L. G. Delogu, and A. Yilmazer. 2020. “A Closer Look at the Genotoxicity of Graphene Based Materials.” Journal of Physics: Materials 3 (1): 014007. https://doi.org/10.1088/2515-7639/ab5844
  • Haase, A., N. Dommershausen, M. Schulz, R. Landsiedel, P. Reichardt, B. C. Krause, J. Tentschert, and A. Luch. 2017. “Genotoxicity Testing of Different Surface-Functionalized SiO2, ZrO2 and Silver Nanomaterials in 3D Human Bronchial Models.” Archives of Toxicology 91 (12): 3991–4007. https://doi.org/10.1007/s00204-017-2015-9
  • Halamoda-Kenzaoui, B., M. Ceridono, P. Colpo, A. Valsesia, P. Urbán, I. Ojea-Jiménez, S. Gioria, D. Gilliland, F. Rossi, and A. Kinsner-Ovaskainen. 2015. “Dispersion Behaviour of Silica Nanoparticles in Biological Media and Its Influence on Cellular Uptake.” PLoS One 10 (10): e0141593. https://doi.org/10.1371/journal.pone.0141593
  • Hiemstra, P. S., G. Grootaers, A. M. van der Does, C. A. M. Krul, and I. M. Kooter. 2018. “Human Lung Epithelial Cell Cultures for Analysis of Inhaled Toxicants: Lessons Learned and Future Directions.” Toxicology in Vitro: An International Journal Published in Association with BIBRA 47: 137–146. https://doi.org/10.1016/j.tiv.2017.11.005
  • Huang, M., Z.-H. Miao, H. Zhu, Y.-J. Cai, W. Lu, and J. Ding. 2008. “Chk1 and Chk2 Are Differentially Involved in Homologous Recombination Repair and Cell Cycle Arrest in Response to DNA Double-Strand Breaks Induced by Camptothecins.” Molecular Cancer Therapeutics 7 (6): 1440–1449. https://doi.org/10.1158/1535-7163.MCT-07-2116
  • Huang, X., and Z. Darzynkiewicz. 2006. Cytometric Assessment of Histone H2AX Phosphorylation. DNA Repair Protocols, 73–80. Berlin, Germany: Springer.
  • Huang, X., M. Okafuji, F. Traganos, E. Luther, E. Holden, and Z. Darzynkiewicz. 2004. “Assessment of Histone H2AX Phosphorylation Induced by DNA Topoisomerase I and II Inhibitors Topotecan and Mitoxantrone and by the DNA Cross‐Linking Agent Cisplatin.” Cytometry. Part A: The Journal of the International Society for Analytical Cytology 58 (2): 99–110. https://doi.org/10.1002/cyto.a.20018
  • Jiao, Z., J. Chang, J. Li, D. Nie, H. Cui, and D. Guo. 2017. “Sulforaphane Increases Nrf2 Expression and Protects Alveolar Epithelial Cells against Injury Caused by Cigarette Smoke Extract.” Molecular Medicine Reports 16 (2): 1241–1247. https://doi.org/10.3892/mmr.2017.6700
  • Jin, Y., S. Kannan, M. Wu, and J. X. Zhao. 2007. “Toxicity of Luminescent Silica Nanoparticles to Living Cells.” Chemical Research in Toxicology 20 (8): 1126–1133. https://doi.org/10.1021/tx7001959
  • Karkossa, I., A. Bannuscher, B. Hellack, A. Bahl, S. Buhs, P. Nollau, A. Luch, K. Schubert, M. von Bergen, and A. Haase. 2019. “An in-Depth Multi-Omics Analysis in RLE-6TN Rat Alveolar Epithelial Cells Allows for Nanomaterial Categorization.” Particle and Fibre Toxicology 16 (1): 38. https://doi.org/10.1186/s12989-019-0321-5
  • Karkossa, I., A. Bannuscher, B. Hellack, W. Wohlleben, J. Laloy, M. S. Stan, A. Dinischiotu, et al. 2021. “Nanomaterials Induce Different Levels of Oxidative Stress, Depending on the Used Model System: Comparison of in Vitro and in Vivo Effects.” The Science of the Total Environment 801: 149538. https://doi.org/10.1016/j.scitotenv.2021.149538
  • Kasper, J. Y., L. Feiden, M. I. Hermanns, C. Bantz, M. Maskos, R. E. Unger, and C. J. Kirkpatrick. 2015. “Pulmonary Surfactant Augments Cytotoxicity of Silica Nanoparticles: Studies on an in Vitro Air–Blood Barrier Model.” Beilstein Journal of Nanotechnology 6: 517–528. https://doi.org/10.3762/bjnano.6.54
  • Kroll, A., C. Dierker, C. Rommel, D. Hahn, W. Wohlleben, C. Schulze-Isfort, C. Göbbert, M. Voetz, F. Hardinghaus, and J. Schnekenburger. 2011. “Cytotoxicity Screening of 23 Engineered Nanomaterials Using a Test Matrix of Ten Cell Lines and Three Different Assays.” Particle and Fibre Toxicology 8 (1): 9. https://doi.org/10.1186/1743-8977-8-9
  • Kroll, A., M. H. Pillukat, D. Hahn, and J. Schnekenburger. 2012. “Interference of Engineered Nanoparticles with in Vitro Toxicity Assays.” Archives of Toxicology 86 (7): 1123–1136. https://doi.org/10.1007/s00204-012-0837-z
  • Kryston, T. B., A. B. Georgiev, P. Pissis, and A. G. Georgakilas. 2011. “Role of Oxidative Stress and DNA Damage in Human Carcinogenesis.” Mutation Research 711 (1–2): 193–201. https://doi.org/10.1016/j.mrfmmm.2010.12.016
  • Kwon, J. Y., P. Koedrith, and Y. R. Seo. 2014. “Current Investigations into the Genotoxicity of Zinc Oxide and Silica Nanoparticles in Mammalian Models in Vitro and in Vivo: Carcinogenic/Genotoxic Potential, Relevant Mechanisms and Biomarkers, Artifacts, and Limitations.” International Journal of Nanomedicine 9 (2): 271–286. https://doi.org/10.2147/IJN.S57918
  • Landsiedel, R., N. Honarvar, S. B. Seiffert, B. Oesch, and F. Oesch. 2022. “Genotoxicity Testing of Nanomaterials.” Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology 14 (6): e1833. https://doi.org/10.1002/wnan.1833
  • Lankoff, A., M. Arabski, A. Wegierek-Ciuk, M. Kruszewski, H. Lisowska, A. Banasik-Nowak, K. Rozga-Wijas, M. Wojewodzka, and S. Slomkowski. 2013. “Effect of Surface Modification of Silica Nanoparticles on Toxicity and Cellular Uptake by Human Peripheral Blood Lymphocytes in Vitro.” Nanotoxicology 7 (3): 235–250. https://doi.org/10.3109/17435390.2011.649796
  • Lu, C., F. Zhu, Y. Y. Cho, F. Tang, T. Zykova, W. Y. Ma, A. M. Bode, and Z. Dong. 2006. “Cell Apoptosis: Requirement of H2AX in DNA Ladder Formation, but Not for the Activation of Caspase-3.” Molecular Cell 23 (1): 121–132. https://doi.org/10.1016/j.molcel.2006.05.023
  • Marzaioli, V., J. A. Aguilar-Pimentel, I. Weichenmeier, G. Luxenhofer, M. Wiemann, R. Landsiedel, W. Wohlleben, et al. 2014. “Surface Modifications of Silica Nanoparticles Are Crucial for Their Inert versus Proinflammatory and Immunomodulatory Properties.” International Journal of Nanomedicine 9: 2815–2832. https://doi.org/10.2147/IJN.S57396
  • Maser, E., M. Schulz, U. G. Sauer, M. Wiemann, L. Ma-Hock, W. Wohlleben, A. Hartwig, and R. Landsiedel. 2015. “In Vitro and in Vivo Genotoxicity Investigations of Differently Sized Amorphous SiO2 Nanomaterials.” Mutation Research. Genetic Toxicology and Environmental Mutagenesis 794: 57–74. https://doi.org/10.1016/j.mrgentox.2015.10.005
  • Mogi, S., and D. H. Oh. 2006. “γ-H2AX Formation in Response to Interstrand Crosslinks Requires XPF in Human Cells.” DNA Repair 5 (6): 731–740. https://doi.org/10.1016/j.dnarep.2006.03.009
  • Moller, P., A. Azqueta, E. Boutet-Robinet, G. Koppen, S. Bonassi, M. Milic, G. Gajski, et al. 2020. “Minimum Information for Reporting on the Comet Assay (MIRCA): Recommendations for Describing Comet Assay Procedures and Results.” Nature Protocols 15 (12): 3817–3826. https://doi.org/10.1038/s41596-020-0398-1
  • Mu, Q., N. S. Hondow, L. Krzemiński, A. P. Brown, L. J. C. Jeuken, and M. N. Routledge. 2012. “Mechanism of Cellular Uptake of Genotoxic Silica Nanoparticles.” Particle and Fibre Toxicology 9 (1): 29. https://doi.org/10.1186/1743-8977-9-29
  • NanoToxClass. 2017. NanoToxClass Standard Operation Procedure - Preparation of Nanoparticle Suspensions by Cup Horn Sonication. https://www.nanopartikel.info/NanoToxClassSOP_Dispersion.
  • Nayl, A. A., A. I. Abd-Elhamid, A. A. Aly, and S. Brase. 2022. “Recent Progress in the Applications of Silica-Based Nanoparticles.” RSC Advances 12 (22): 13706–13726. https://doi.org/10.1039/d2ra01587k
  • Nikolova, T., F. Marini, and B. Kaina. 2017. “Genotoxicity Testing: Comparison of the gammaH2AX Focus Assay with the Alkaline and Neutral Comet Assays.” Mutation Research. Genetic Toxicology and Environmental Mutagenesis 822: 10–18. https://doi.org/10.1016/j.mrgentox.2017.07.004
  • Oberdorster, G., A. Maynard, K. Donaldson, V. Castranova, J. Fitzpatrick, K. Ausman, J. Carter, et al. 2005. “Principles for Characterizing the Potential Human Health Effects from Exposure to Nanomaterials: elements of a Screening Strategy.” Particle and Fibre Toxicology 2 (1): 8. https://doi.org/10.1186/1743-8977-2-8
  • Oda, K., R. Yumoto, J. Nagai, H. Katayama, and M. Takano. 2011. “Mechanism Underlying Insulin Uptake in Alveolar Epithelial Cell Line RLE-6TN.” European Journal of Pharmacology 672 (1–3): 62–69. https://doi.org/10.1016/j.ejphar.2011.10.003
  • OECD. 2014. “Genotoxicity of Manufactured Nanomaterials: Report of the Oecd Expert.” Series on the Safety of Manufactured Nanomaterials. Paris, France: OECD.
  • OECD. 2016a. Test No. 473: In Vitro Mammalian Chromosomal Aberration Test. Paris, France: OECD.
  • OECD. 2016b. Test No. 476: In Vitro Mammalian Cell Gene Mutation Tests Using the Hprt and Xprt Genes. Paris, France: OECD.
  • OECD. 2016c. Test No. 487: In Vitro Mammalian Cell Micronucleus Test. Paris, France: OECD.
  • OECD. 2016d. Test No. 490: In Vitro Mammalian Cell Gene Mutation Tests Using the Thymidine Kinase Gene. Paris, France: OECD.
  • Pauluhn, J. 2009. “Comparative Pulmonary Response to Inhaled Nanostructures: considerations on Test Design and Endpoints.” Inhalation Toxicology 21 (1): 40–54. https://doi.org/10.1080/08958370902962291
  • Pietroiusti, A., H. Stockmann-Juvala, F. Lucaroni, and K. Savolainen. 2018. “Nanomaterial Exposure, Toxicity, and Impact on Human Health.” Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology 10 (5): e1513. https://doi.org/10.1002/wnan.1513
  • Podhorecka, M., A. Skladanowski, and P. Bozko. 2010. “H2AX Phosphorylation: Its Role in DNA Damage Response and Cancer Therapy.” Journal of Nucleic Acids 2010: 1–9. https://doi.org/10.4061/2010/920161
  • Rogakou, E. P., W. Nieves-Neira, C. Boon, Y. Pommier, and W. M. Bonner. 2000. “Initiation of DNA Fragmentation during Apoptosis Induces Phosphorylation of H2AX Histone at Serine 139.” The Journal of Biological Chemistry 275 (13): 9390–9395. https://doi.org/10.1074/jbc.275.13.9390
  • Rogakou, E. P., D. R. Pilch, A. H. Orr, V. S. Ivanova, and W. M. Bonner. 1998. “DNA Double-Stranded Breaks Induce Histone H2AX Phosphorylation on Serine 139.” The Journal of Biological Chemistry 273 (10): 5858–5868. https://doi.org/10.1074/jbc.273.10.5858
  • Rosário, F., M. J. Bessa, F. Brandão, C. Costa, C. B. Lopes, A. C. Estrada, D. S. Tavares, J. P. Teixeira, and A. T. Reis. 2020. “Unravelling the Potential Cytotoxic Effects of Metal Oxide Nanoparticles and Metal (Loid) Mixtures on A549 Human Cell Line.” Nanomaterials 10 (3): 447. https://doi.org/10.3390/nano10030447
  • Scarpato, R., S. Castagna, R. Aliotta, A. Azzara, F. Ghetti, E. Filomeni, C. Giovannini, et al. 2013. “Kinetics of Nuclear Phosphorylation (gamma-H2AX) in Human Lymphocytes Treated in Vitro with UVB, Bleomycin and Mitomycin C.” Mutagenesis 28 (4): 465–473. https://doi.org/10.1093/mutage/get024
  • Schonn, I., J. Hennesen, and D. C. Dartsch. 2010. “Cellular Responses to Etoposide: Cell Death despite Cell Cycle Arrest and Repair of DNA Damage.” Apoptosis: An International Journal on Programmed Cell Death 15 (2): 162–172. https://doi.org/10.1007/s10495-009-0440-9
  • Shang, L., K. Nienhaus, and G. U. Nienhaus. 2014. “Engineered Nanoparticles Interacting with Cells: Size Matters.” Journal of Nanobiotechnology 12 (1): 5. https://doi.org/10.1186/1477-3155-12-5
  • Shatkin, J. A. 2008. Introduction: Assessing Nanotechnology Health and Environmental Risks. Nanotechnology, 21–40. Boca Raton, FL:CRC Press.
  • Skuland, T., J. Øvrevik, M. Låg, and M. Refsnes. 2014. “Role of Size and Surface Area for Pro-Inflammatory Responses to Silica Nanoparticles in Epithelial Lung Cells: Importance of Exposure Conditions.” Toxicology in Vitro: An International Journal Published in Association with BIBRA 28 (2): 146–155. https://doi.org/10.1016/j.tiv.2013.10.018
  • Smith, J., L. M. Tho, N. Xu, and D. A. Gillespie. 2010. “The ATM-Chk2 and ATR-Chk1 Pathways in DNA Damage Signaling and Cancer.” Advances in Cancer Research 108: 73–112. https://doi.org/10.1016/B978-0-12-380888-2.00003-0
  • Stone, V., M. R. Miller, M. J. D. Clift, A. Elder, N. L. Mills, P. Moller, R. P. F. Schins, et al. 2017. “Nanomaterials versus Ambient Ultrafine Particles: An Opportunity to Exchange Toxicology Knowledge.” Environmental Health Perspectives 125 (10): 106002. https://doi.org/10.1289/EHP424
  • Swedish Chemicals Agency. 2016. Report 13/16 Nanomaterials and Genotoxicity - a Literature Review, ISSN 0284-1185. Article number: 361 218.
  • Tanaka, T., A. Kurose, X. Huang, W. Dai, and Z. Darzynkiewicz. 2006. “ATM Activation and Histone H2AX Phosphorylation as Indicators of DNA Damage by DNA Topoisomerase I Inhibitor Topotecan and during Apoptosis.” Cell Proliferation 39 (1): 49–60. https://doi.org/10.1111/j.1365-2184.2006.00364.x
  • Tomilin, N., L. Solovjeva, M. Svetlova, N. Pleskach, I. Zalenskaya, P. Yau, and E. Bradbury. 2001. “Visualization of Focal Nuclear Sites of DNA Repair Synthesis Induced by Bleomycin in Human Cells.” Radiation Research 156 (4): 347–354. https://doi.org/10.1667/0033-7587(2001)156[0347:VOFNSO2.0.CO;2]
  • Tsuji, J. S., A. D. Maynard, P. C. Howard, J. T. James, C. W. Lam, D. B. Warheit, and A. B. Santamaria. 2006. “Research Strategies for Safety Evaluation of Nanomaterials, Part IV: risk Assessment of Nanoparticles.” Toxicological Sciences: An Official Journal of the Society of Toxicology 89 (1): 42–50. https://doi.org/10.1093/toxsci/kfi339
  • Uboldi, C., G. Giudetti, F. Broggi, D. Gilliland, J. Ponti, and F. Rossi. 2012. “Amorphous Silica Nanoparticles Do Not Induce Cytotoxicity, Cell Transformation or Genotoxicity in Balb/3T3 Mouse Fibroblasts.” Mutation Research 745 (1–2): 11–20. https://doi.org/10.1016/j.mrgentox.2011.10.010
  • Valdiglesias, V., S. Giunta, M. Fenech, M. Neri, and S. Bonassi. 2013. “γH2AX as a Marker of DNA Double Strand Breaks and Genomic Instability in Human Population Studies.” Mutation Research 753 (1): 24–40. https://doi.org/10.1016/j.mrrev.2013.02.001
  • Valdiglesias, V., B. Laffon, E. Pásaro, and J. Méndez. 2011. “Evaluation of Okadaic Acid-Induced Genotoxicity in Human Cells Using the Micronucleus Test and γH2AX Analysis.” Journal of Toxicology and Environmental Health. Part A 74 (15–16): 980–992. https://doi.org/10.1080/15287394.2011.582026
  • Vance, M. E., T. Kuiken, E. P. Vejerano, S. P. McGinnis, M. F. Hochella, Jr., D. Rejeski, and M. S. Hull. 2015. “Nanotechnology in the Real World: Redeveloping the Nanomaterial Consumer Products Inventory.” Beilstein Journal of Nanotechnology 6: 1769–1780. https://doi.org/10.3762/bjnano.6.181
  • Wan, R., Y. Mo, R. Tong, M. Gao, and Q. Zhang. 2019. “Determination of Phosphorylated Histone H2AX in Nanoparticle-Induced Genotoxic Studies.” Methods in Molecular Biology 1894: 145–159. https://doi.org/10.1007/978-1-4939-8916-4_9
  • Ward, I. M., and J. Chen. 2001. “Histone H2AX is Phosphorylated in an ATR-Dependent Manner in Response to Replicational Stress.” The Journal of Biological Chemistry 276 (51): 47759–47762. https://doi.org/10.1074/jbc.C100569200
  • Wiemann, M., A. Vennemann, U. G. Sauer, K. Wiench, L. Ma-Hock, and R. Landsiedel. 2016. “An in Vitro Alveolar Macrophage Assay for Predicting the Short-Term Inhalation Toxicity of Nanomaterials.” Journal of Nanobiotechnology 14 (1): 16. https://doi.org/10.1186/s12951-016-0164-2
  • Wiemann, M., A. Vennemann, T. B. Schuster, J. Nolde, and N. Krueger. 2022. “Surface Treatment with Hydrophobic Coating Reagents (Organosilanes) Strongly Reduces the Bioactivity of Synthetic Amorphous Silica in Vitro.” Frontiers in Public Health 10: 902799. https://doi.org/10.3389/fpubh.2022.902799
  • Wiemann, M., A. Vennemann, C. Venzago, G. G. Lindner, T. B. Schuster, and N. Krueger. 2021. “Serum Lowers Bioactivity and Uptake of Synthetic Amorphous Silica by Alveolar Macrophages in a Particle Specific Manner.” Nanomaterials 11 (3): 628. https://doi.org/10.3390/nano11030628
  • Wohlleben, W., M. D. Driessen, S. Raesch, U. F. Schaefer, C. Schulze, B. Vacano, A. Vennemann, et al. 2016. “Influence of Agglomeration and Specific Lung Lining Lipid/Protein Interaction on Short-Term Inhalation Toxicity.” Nanotoxicology 10 (7): 970–980. https://doi.org/10.3109/17435390.2016.1155671
  • Yazdimamaghani, M., P. J. Moos, M. A. Dobrovolskaia, and H. Ghandehari. 2019. “Genotoxicity of Amorphous Silica Nanoparticles: Status and Prospects.” Nanomedicine: Nanotechnology, Biology, and Medicine 16: 106–125. https://doi.org/10.1016/j.nano.2018.11.013
  • Yoshida, T., Y. Yoshioka, K. Matsuyama, Y. Nakazato, S. Tochigi, T. Hirai, S. Kondoh, et al. 2012. “Surface Modification of Amorphous Nanosilica Particles Suppresses Nanosilica-Induced Cytotoxicity, ROS Generation, and DNA Damage in Various Mammalian Cells.” Biochemical and Biophysical Research Communications 427 (4): 748–752. https://doi.org/10.1016/j.bbrc.2012.09.132
  • Zhang, H., D. R. Dunphy, X. Jiang, H. Meng, B. Sun, D. Tarn, M. Xue, et al. 2012. “Processing Pathway Dependence of Amorphous Silica Nanoparticle Toxicity: Colloidal vs Pyrolytic.” Journal of the American Chemical Society 134 (38): 15790–15804. https://doi.org/10.1021/ja304907c