Intrinsic toxicity of stable nanosized titanium dioxide using polyacrylate in human keratinocytes

다국어 초록 (Multilingual Abstract)

Backgrounds: Trends in the use of an anticoagulant as a dispersing stabilizer are addressed. An effective approach to preparing stable nanosized titanium dioxide (nTiO2) for accurate and systematic assessment of nano- toxicity has not been established.
Methods: Among the dispersants tested here, it was found that sodium polyacrylate (PAA) was the most effective dispersant for nTiO2 in culture media. Our study was the first to demonstrate that a stable PAA-dispersed nTiO2 (nTiO2/PAA) suspension showed more toxic than nTiO2 without PAA in human HaCaT keratinocytes.
Results: Initially, MTT results showed that the stable nTiO2/PAA dispersion exhibited significantly greater cytotoxicity than nTiO2 without PAA. In addition, the stable nTiO2/PAA dispersion induced markedly more oxidative stress than nTiO2 without PAA. Importantly, the stable nTiO2/PAA dispersion caused DNA breakage to a greater extent than nTiO2 without PAA.
Conclusion: Our findings indicated that the anti-coagulant PAA is suitable for preparing homologous dispersed nTiO2 under realistic physiological culture test conditions.

참고문헌 (Reference)

1 Yamamoto, F., "Ubiquitous presence in mammalian cells of enzymatic activity specifically cleaving 8-hydroxyguanine-containing DNA" 83 : 351-357, 1992

2 Federici, G., "Toxicity of titanium dioxide nanoparticles to rainbow trout (Oncorhynchus mykiss): gill injury, oxidative stress, and other physiological effects" 84 : 415-430, 2007

3 Hext, P. M., "Titanium dioxide: inhalation toxicology and epidemiology" 49 : 461-472, 2005

4 Kang, S. J., "Titanium dioxide nanoparticles trigger p53-mediated damage response in peripheral blood lymphocytes" 49 : 399-405, 2008

5 Bhattacharya, K., "Titanium dioxide nanoparticles induce oxidative stress and DNA-adduct formation but not DNA-breakage in human lung cells" 6 : 17-, 2009

6 Trouiller, B., "Titanium dioxide nanoparticles induce DNA damage and genetic instability in vivo in mice" 69 : 8784-8789, 2009

7 Smijs, T. G., "Titanium dioxide and zinc oxide nanoparticles in sunscreens: focus on their safety and effectiveness" 4 : 95-112, 2011

8 Crosera, M., "Titanium Dioxide Nanoparticle Penetration into the Skin and Effects on HaCaT Cells" 12 : 9282-9297, 2015

9 Dick, C. A. J., "The role of free radicals in the toxic and inflammatory effects of four different ultrafine particle types" 15 : 39-52, 2003

10 Fairbairn, D. W., "The neutral comet assay is sufficient to identify an apoptotic 'window' by visual inspection" 1 : 91-94, 1996

11 Spielmann, H., "The International EU/COLIPA In Vitro Phototoxicity Validation Study: Results of phase II (blind trial). Part 1. The 3T3 NRU phototoxicity test" 12 : 305-327, 1998

12 Spielmann, H., "Successful validation of in vitro methods in toxicology by ZEBET, the National Centre for Alternatives in Germany at the BfR (Federal Institute for Risk Assessment)" 60 : 225-233, 2008

13 Nohynek, G. J., "Safety assessment of personal care products/cosmetics and their ingredients" 243 : 239-259, 2010

14 Saito, S., "Quantitative determination of urinary 8-hydroxydeoxyguanosine (8-OH-dG) by using ELISA" 107 : 39-44, 2000

15 Park, J., "Protective role of thioredoxin reductase 1 in cadmium-induced DNA damage" 8 : 289-295, 2012

16 Rideh, L., "Photocatalytic degradation of 2-chlorophenol in TiO2 aqueous suspension: Modeling of reaction rate" 36 : 4712-4718, 1997

17 Linsebigler, A. L., "Photocatalysis on TiO2 Surfaces-Principles, Mechanisms, and Selected Results" 95 : 735-758, 1995

18 Jaeger, A., "Oxidative stress-induced cytotoxic and genotoxic effects of nano-sized titanium dioxide particles in human Ha-CaT keratinocytes" 296 : 27-36, 2012

19 Borrego, S., "Oxidative Stress and DNA Damage in Human Gastric Carcinoma: 8-Oxo-7'8-dihydro-2'-deoxyguanosine (8-oxo-dG) as a Possible Tumor Marker" 14 : 3467-3486, 2013

20 Oberdorster, G., "Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles" 113 : 823-839, 2005

21 Nohynek, G. J., "Nanotechnology, cosmetics and the skin: is there a health risk?" 21 : 136-149, 2008

22 Hackenberg, S., "Nanosized titanium dioxide particles do not induce DNA damage in human peripheral blood lymphocytes" 52 : 264-268, 2011

23 Hoet, P. H., "Nanoparticles-known and unknown health risks" 2 : 12-, 2004

24 Lee, J., "Nanomaterials in the construction industry: a review of their applications and environmental health and safety considerations" 4 : 3580-3590, 2010

25 Singh, N., "NanoGenotoxicology: the DNA damaging potential of engineered nanomaterials" 30 : 3891-3914, 2009

26 Xue, C., "Nano titanium dioxide induces the generation of ROS and potential damage in HaCaT cells under UVA irradiation" 10 : 8500-8507, 2010

27 R ehn, B., "Investigations on the inflammatory and genotoxic lung effects of two types of titanium dioxide: untreated and surface treated" 189 : 84-95, 2003

28 Tanaka, S., "Increased hepatic oxidative DNA damage in patients with nonalcoholic steatohepatitis who develop hepatocellular carcinoma" 48 : 1249-1258, 2013

29 Hamzeh, M., "In vitro cytotoxicity and genotoxicity studies of titanium dioxide ($TiO_{2}$) nanoparticles in Chinese hamster lung fibroblast cells" 27 : 864-873, 2013

30 Jassby, D., "Impact of aggregate size and structure on the photocatalytic properties of $TiO_{2}$ and ZnO nanoparticles" 46 : 6934-6941, 2012

31 Schilling, K., "Human safety review of nano titanium dioxide and zinc oxide" 9 : 495-509, 2010

32 Taneja, N., "Histone H2AX phosphorylation as a predictor of radiosensitivity and target for radiotherapy" 279 : 2273-2280, 2004

33 Jha, A. N., "Genotoxic effects of sodium arsenite on human cells" 284 : 215-221, 1992

34 Gallagher, J., "Formation of DNA adducts in rat lung following chronic inhalation of diesel emissions, carbon black and titanium dioxide particles" 15 : 1291-1299, 1994

35 Koedrith, P., "Enhancement of the efficacy of mitomycin C-mediated apoptosis in human colon cancer cells with RNAi-based thioredoxin reductase 1 deficiency" 2 : 873-878, 2011

36 Wright, C., "Effects of titanium dioxide nanoparticles on human keratinocytes" 40 : 90-100, 2017

37 Prasad, R. Y., "Effect of treatment media on the agglomeration of titanium dioxide nanoparticles: impact on genotoxicity, cellular interaction, and cell cycle" 7 : 1929-1942, 2013

38 Lopes, V. R., "Dose-dependent autophagic effect of titanium dioxide nanoparticles in human HaCaT cells at non-cytotoxic levels" 14 : 22-, 2016

39 Warheit, D. B., "Development of a base set of toxicity tests using ultrafine $TiO_{2}$ particles as a component of nanoparticle risk management" 171 : 99-110, 2007

40 Kang, J. L., "Comparison of the biological activity between ultrafine and fine titanium dioxide particles in RAW 264.7 cells associated with oxidative stress" 71 : 478-485, 2008

41 Xia, T., "Comparison of the abilities of ambient and manufactured nanoparticles to induce cellular toxicity according to an oxidative stress paradigm" 6 : 1794-1807, 2006

42 Rahmani, M., "Coadministration of histone deacetylase inhibitors and perifosine synergistically induces apoptosis in human leukemia cells through Akt and ERK1/2 inactivation and the generation of ceramide and reactive oxygen species" 65 : 2422-2432, 2005

43 Hartwig, A, "Carcinogenicity of metal compounds: possible role of DNA repair inhibition" 103 : 235-239, 1998

44 Baan, R., "Carcinogenicity of carbon black, titanium dioxide, and talc" 7 : 295-296, 2006

45 Pons, T., "Cadmium-free CuInS2/ZnS quantum dots for sentinel lymph node imaging with reduced toxicity" 4 : 2531-2538, 2010

46 Gelis, C., "Assessment of the skin photoprotective capacities of an organo-mineral broad-spectrum sunblock on two ex vivo skin models" 19 : 242-253, 2003

47 McCall, M. J., "A tiered approach" 8 : 307-308, 2013

48 Wojewodzka, M., "A modified neutral comet assay: elimination of lysis at high temperature and validation of the assay with anti-single-stranded DNA antibody" 518 : 9-20, 2002

49 Buford, M. C., "A comparison of dispersing media for various engineered carbon nanoparticles" 4 : 6-, 2007

50 Valavanidis, A., "8-hydroxy-2'-deoxyguanosine (8-OHdG): A Critical Biomarker of Oxidative Stress and Carcinogenesis" 27 : 120-139, 2009