Genotoxicity of Two Nanoparticles: Titanium Dioxide and Zinc Oxide

Abstract

Nanoparticles (NPs) and nanoparticle-based materials have been increasingly used in various consumer and medical applications. However, investigations have disclosed that some NPs may generate toxic effects in different cell types and organisms. In this study, the cytotoxic and genotoxic potential of titanium dioxide (TiO2) and zinc oxide (ZnO) NPs were examined by using four genotoxicity tests, chromosome aberrations-CAs, sister chromatid exchange-SCE, micronucleus-MN, and comet, in human lymphocytes in vitro. The results showed that both NPs significantly increased the frequency of aberrant cells, CA/Cell, SCE, and DNA damage, and decreased mitotic index in some treatments. These results demonstrated that TiO2 and ZnO NPs induce genotoxic effects. Therefore, more detailed in vitro and in vivo experiments should be conducted for the safe usage of both NPs.

Keywords

• Titanium dioxide nanoparticles
• Zinc oxide nanoparticles
• Chromosome aberration test
• Micronucleus test
• Comet assay

References

1. [1] Baranowska-Wójcik, E., Szwajgier, D., Oleszczuk, P., Winiarska-Mieczan, A., “Effects of titanium dioxide nanoparticles exposure on human health-a review”, Biological Trace Element Research, 193:118-129, (2020).
2. [2] Osmond M.J., MacCall, J., “Zinc oxide nanoparticles in modern sunscreens: an analysis of potential exposure and hazard”, Nanotoxicology 4:15-41, (2010).
3. [3] Ramimoghadam, D., Bin Hussein, M.Z., Taufiq-Yap, Y.H. “Hydrothermal synthesis of zinc oxide nanoparticles using rice as soft biotemplate”, Chemistry Central Journal 7: 136, (2013).
4. [4] Jiang, J, Pi, J., Cai, J., “The advancing of zinc oxide nanoparticles for biomedical applications”, Bioinorganic Chemistry and Applications 3:1-18, (2018).
5. [5] Singh, S., “Zinc oxide nanoparticles impacts: Cytotoxicity, genotoxicity, developmental toxicity, and neurotoxicity”, Toxicology Mechanisms and Methods, 29: 300-311, (2019).
6. [6] Acar, M.S., Bulut Z.B., Ates, A., Nami, B., Koçak, N., Yildiz, B., "Titanium dioxide nanoparticles induce cytotoxicity and reduce mitotic index in human amniotic fluid-derived cells", Human and Experimental Toxicology, 34:174-182, (2015).
7. [7] Akbaba, G.B., Türkez, H., “Investigation of the genotoxicity of aluminum oxide, β-tricalcium phosphate, and zinc oxide nanoparticles in vitro”, International Journal of Toxicology, 37:216-222, (2018).
8. [8] Bhattacharya, D., Santra; C.R., Ghosh, A.N., Karmakar, P., “Differential toxicity of rod and spherical zinc oxide nanoparticles on human peripheral blood mononuclear cells”, Journal of Biomedical Nanotechnology, 10:707-716, (2014).

9. [9] Jugan, M.L., Barillet, S., Simon-Deckers, A., Herlin-Boime, N., Sauvaigo, S., Douki, T., Carriere, M., “Titanium dioxide nanoparticles exhibit genotoxicity and impair DNA repair activity in A549 cells”, Nanotoxicology, 6:501-513, (2012).
10. [10] Khan, M., Naqvi, A.H., Ahmad, M., “Comparative study of the cytotoxic and genotoxic potentials of zinc oxide and titanium dioxide nanoparticles”, Toxicology Reports, 2:765-774, (2015).
11. [11] Chakrabarti, S., Goyary, D., Karmakar, S., Chattopadhyay, P., “Exploration of cytotoxic and genotoxic endpoints following sub-chronic oral exposure to titanium dioxide nanoparticles”, Toxicology and Industrial Health, 35: 577-592, (2019).
12. [12] Fadoju, O.M., Osinowo, O.A., Ogunsuyi O.I., Oyeyemi, I.T., ; Alabi, O.A., Alimba, C.G., Bakare, A.A., “Interaction of titanium dioxide and zinc oxide nanoparticles induced cytogenotoxicity in Allium cepa”, The Nucleus, 63:159-166, (2020).
13. [13] Ghosh, M., Sinha, S., Jothiramajayam, M., Jana, A., Nag, A., Mukherjee, A., “Cyto-genotoxicity and oxidative stress induced by zinc oxide nanoparticle in human lymphocyte cells in vitro and Swiss albino male mice in vivo”, Food and Chemical Toxicology, 97: 286-296, (2016).
14. [14] Kazimirova, A., Baranokova, M., Staruchova, M., Drlickova, M., Volkovova, K., Dusinska, M. “Titanium dioxide nanoparticles tested for genotoxicity with the comet and micronucleus assays in vitro, ex vivo and in vivo”, Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 843:57-65, (2019).
15. [15] Bhattacharya, K., Davoren, M., Boertz, J., Schins, R.P., Hoffmann, E., Dopp, E., “Titanium dioxide nanoparticles induce oxidative stress and DNA-adduct formation but not DNA-breakage in human lung cells”, Particle and Fibre Toxicology, 6: 17-27, (2009).
16. [16] Hackenberg, S., Friehs, G., Kessler, M., Froelich, K., Ginzkey, C., Koehler, C., Scherzed, A., Burghartz, M., Kleinsaaer, N., "Nanosized titanium dioxide do not Induce DNA damage in human peripheral blood lymphocytes", Environmental and Molecular Mutagenesis, 52: 264-268, (2011).
17. [17] Kwon, J.Y., Lee, S.Y., Koedrith, P., Lee, Y.J., Kim, K.M., Oh, J.M., Yang, S.I., Kim, M.K., Lee, J.K., Jeong, J., Maeng, E.H., Lee, B.J., Seo, Y.R., “Lack of genotoxic potential of ZnO nanoparticles in vitro and in vivo tests”, Mutatation Research/Genetic Toxicology and Environmental Mutagenesis, 761: 1-9, (2014).
18. [18] Evans, H.J., “Human peripheral blood lymphocytes for the analysis of chromosome aberrations in mutagen tests”. In: Kilbey, B.J., Legator, M., Nichols, W., Ramel, C. (Eds.), Handbook of Mutagenicity Test Procedures, 2nd ed. Elsevier Sciences, Amsterdam, 405-424, (1984).
19. [19] Perry, P., Wolff, S. “New Giemsa method for the differential staining of sister chromatids. Nature 251: 156-158, (1974).
20. [20] Speit, G., Haupter, S., "On the mechanism of differential Giemsa staining of bromodeoxyuridine-substituted chromosomes", Human Genetics, 70: 126-129, (1985).
21. [21] Zengin, N., Yuzbasioglu, D., Unal, F., Yilmaz, S., Aksoy, H., “The evaluation of the genotoxicity of two food preservatives: Sodium benzoate and potassium benzoate”, Food and Chemical Toxicology, 49: 763-769, (2011).
22. [22] Surrales, J., Xamena, N., Creus, A., “Induction of micronuclei by five pyrethroid insecticides in whole-blood and isolated human lymphocyte cultures”, Mutation Research, 341: 169-184 (1995).
23. [23] Singh, N.P., McCoy, M.T., Tice, R.R., Schneider, E.L., “A simple technique for quantitation of low levels of DNA damage in individual cells”, Experimental Cell Research, 175: 184-191, (1988).
24. [24] Hackenberg, S., Friehs, G., Kessler, M., Froelich, K., Ginzkey, C., Koehler, C., Scherzed, A., Burghartz, M., Kleinsaaer, N., “Nanosized titanium dioxide do not induce DNA damage in human peripheral blood lymphocytes”, Environmental and Molecular Mutagenesis, 52:264-268, (2011).
25. [25] Patel, S., Patel, P., Bakshi, S.R., “Titanium dioxide nanoparticles: an in vitro study of DNA binding, chromosome aberration assay, and comet assay”, Cytotechnology, 69: 245-263, (2017).
26. [26] Magdolenova, Z., Collins, A., Kumar, A., Dhawan, A., Stone, V., Dusinska, M., “Mechanisms of genotoxicity. A review of in vitro and in vivo studies with engineered nanoparticles”, Nanotoxicology, 8:233-278, (2014).
27. [27] Kwon, J.Y., Koedrith, P., Seo, Y.R., “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, 9:271-286, (2014).
28. [28] Hradil, J., Pisarev, A., Babic, M., Horak, D., “Dextran-modified iron oxide nanoparticles”, China Particulogy, 5:162-168, (2008).
29. [29] Lopez-Leon, T., Ortega-Vinuesa, J.L., Bastos-Gonzalez, D., Elaïssari, A., “Cationic and anionic poly(n-isopropylacrylamide) based submicron gel particles:electrokinetic properties and colloidal stability”, The Journal Physical Chemistry B, 110: 4629-4636, (2006).
30. [30] Vallabani, N.V.S., Shukla, R.K., Konka, D., Kumar, A., Singh, S., Dhawan, A., “TiO2 nanoparticles induced micronucleus formation in human liver (HepG2) cells: comparison of conventional and flow cytometry-based methods”, Molecular Cytogenetics, 7: P79, (Suppl 1) (2014).
31. [31] Chandirasekar, R., Kumar, B.L., Sasikala, K., Jayakumar, R., Suresh, K., Venkatesan, R., Jacob, R., Krishnapriya, E.K., Kavitha, H., Ganesh G.K., “Assessment of genotoxic and molecular mechanisms of cancer risk in smoking and smokeless tobacco users”, Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 767: 21-27, (2014).
32. [32] Maffei, F., Moraga, J.M.Z., Angelini, S., Zenesini, C., Musti, M., Festi, D., Cantelli-Forti, G., Hrelia, P., “Micronucleus frequency in human peripheral blood lymphocytes as a biomarker for the early detection of colorectal cancer risk”, Mutagenesis, 29:221-225, (2014).
33. [33] Ghosh, M., Chakraborty, V. Mukherjee, A., “Cytotoxic, genotoxic, and the hemolytic effect of titanium dioxide (TiO2) nanoparticles on human erythrocyte and lymphocyte cells in vitro”, Journal of Applied Toxicology, 33:1097-1110, (2013). [34] Karlsson, H.L., Di Bucchianico, S., Collins, A.R., Dusinska, M., “Can the comet assay be used reliably to detect nanoparticle‐induced genotoxicity?”, Environmental and Molecular Mutagenesis, 56: 82-96, (2015).
34. [35] Catalán, J., Järventaus, H., Vippola, M., Savolainen, K., Norppa, H., “Induction of chromosomal aberrations by carbon nanotubes and titanium dioxide nanoparticles in human lymphocytes in vitro”, Nanotoxicology, 6:825-836, (2012).
35. [36] Gea, M., Bonetta, S., Iannarelli, L., Giovannozzi, A.M., Maurino, V., Bonetta, S., Hodoroaba, V.S., Armato, C., Rossi, A.M., Schilirò, T., “Shape-engineered titanium dioxide nanoparticles (TiO2-NPs): cytotoxicity and genotoxicity in bronchial epithelial cells”, Food and Chemical Toxicology, 127:89-100, (2019).
36. [37] Prasad, R.Y., Wallace, K., Daniel, K.M., Tennant, A.H., Zucker, R.M., Strickland, J., Dreher, K., Klingerman, A.D., Blackman, C.F., De Marini, D.M., “Effect of treatment media on the agglomeration of titanium dioxide nanoparticles: impact on genotoxicity, cellular interaction, and cell cycle”, ACS Nano, 7:1929-1942, (2013).
37. [38] Proquin, H., Rodriguez-Ibarra, C., Moonen, C.G.J., Urrutia Ortega, I.M., Briede, J.J., de Kok, T.M., van Loveren, H., Chirino, Y.I., “Titanium dioxide food additive (E171) induces ROS formation and genotoxicity: contribution of micro and nanosized fractions”, Mutagenesis, 32:139-149, (2017).
38. [39] Piperakis, S.M., “Comet assay: A brief history”, Cell Biology and Toxicology, 25: 1-3, (2009).
39. [40] Charles, S., Jomini, S., Fessard, V., Bigorgne-Vizade, E., Rousselle, C., Michel, C., “Assessment of the in vitro genotoxicity of TiO2 nanoparticles in a regulatory context”, Nanotoxicology, 12: 357-374, (2018).