CeO2 nanoparticles induce DNA damage towards human dermal fibroblasts in vitro

Cerium dioxide nanoparticles have been proposed for an increasing number of applications in biomedicine, cosmetic, as polishing materials and also as byproducts from automotive fuel additives. The aim of this study was to examine the potential in vitro cyto- and genotoxicity of nano-sized CeO2 (7 nm) on human dermal fibroblasts. By combining a physico-chemical and a (geno)toxicological approach, we defined the causal mechanisms linking the physico-chemical properties of nano-CeO2 with their biological effects. Using X-ray absorption spectroscopy, we observed a reduction of 21±4% of the Ce4+ atoms localized at the surface of CeO2 nanoparticles due to the interactions with organic molecules present in biological media. These particles induced strong DNA lesions and chromosome damage related to an oxidative stress. These genotoxic effects occurred at very low doses, which highlighted the importance of a genotoxicological approach during the assessment of the toxicity of nanoparticles.

[1]  Susannah L. Scott,et al.  The effect of cryogenic sample cooling on X-ray absorption spectra , 2005 .

[2]  Jinhee Choi,et al.  Oxidative stress induced by cerium oxide nanoparticles in cultured BEAS-2B cells. , 2008, Toxicology.

[3]  Alain Michalowicz EXAFS pour le MAC : A new version of an EXAFS Data analysis code for the Macintosh , 1997 .

[4]  J. West,et al.  Correlating nanoscale titania structure with toxicity: a cytotoxicity and inflammatory response study with human dermal fibroblasts and human lung epithelial cells. , 2006, Toxicological sciences : an official journal of the Society of Toxicology.

[5]  B. Sanderson,et al.  Cytotoxicity and genotoxicity of ultrafine crystalline SiO2 particulate in cultured human lymphoblastoid cells , 2007, Environmental and molecular mutagenesis.

[6]  J. Hazemann,et al.  FAME: a new beamline for x-ray absorption investigations of very-diluted systems of environmental, material and biological interests , 2005 .

[7]  P. Verrando,et al.  Evaluation of Sunscreen Protection in Human Melanocytes Exposed to UVA or UVB Irradiation Using the Alkaline Comet Assay ¶ , 2001, Photochemistry and photobiology.

[8]  Mark R Wiesner,et al.  In vitro interactions between DMSA-coated maghemite nanoparticles and human fibroblasts: A physicochemical and cyto-genotoxical study. , 2006, Environmental science & technology.

[9]  S. Trasatti,et al.  The Point of Zero Charge of CeO2 , 1994 .

[10]  M. Nolan,et al.  Oxygen vacancy formation and migration in ceria , 2006 .

[11]  R. Tarnuzzer,et al.  Vacancy engineered ceria nanostructures for protection from radiation-induced cellular damage. , 2005, Nano letters.

[12]  Franck Chauvat,et al.  Cytotoxicity of CeO2 nanoparticles for Escherichia coli. Physico-chemical insight of the cytotoxicity mechanism. , 2006, Environmental science & technology.

[13]  P. Verrando,et al.  Evaluation of Sunscreen Protection in Human Melanocytes Exposed to UVA or UVB Irradiation Using the Alkaline Comet Assay¶ , 2001 .

[14]  Navid B. Saleh,et al.  Titanium dioxide (P25) produces reactive oxygen species in immortalized brain microglia (BV2): implications for nanoparticle neurotoxicity. , 2006, Environmental science & technology.

[15]  K. Fukui,et al.  Imaging of surface oxygen atoms and their defect structures on CeO2(1 1 1) by noncontact atomic force microscopy , 2002 .

[16]  L. Rogers,et al.  Cardioprotective effects of cerium oxide nanoparticles in a transgenic murine model of cardiomyopathy. , 2007, Cardiovascular research.

[17]  Zissis Samaras,et al.  Hazard and risk assessment of a nanoparticulate cerium oxide-based diesel fuel additive - a case study. , 2008, Inhalation toxicology.

[18]  H. Arwin,et al.  A spectroscopic ellipsometry study of cerium dioxide thin films grown on sapphire by rf magnetron sputtering , 1995 .

[19]  B. Cabane,et al.  Growth of colloidal aggregates through polymer bridging , 1993 .

[20]  H. Bartsch,et al.  Chronic inflammation and oxidative stress in the genesis and perpetuation of cancer: role of lipid peroxidation, DNA damage, and repair , 2006, Langenbeck's Archives of Surgery.

[21]  David Schubert,et al.  Cerium and yttrium oxide nanoparticles are neuroprotective. , 2006, Biochemical and biophysical research communications.

[22]  G. Duménil,et al.  Evaluation of photolyase (Photosome) repair activity in human keratinocytes after a single dose of ultraviolet B irradiation using the comet assay. , 2005, Journal of photochemistry and photobiology. B, Biology.

[23]  M. Das,et al.  Auto-catalytic ceria nanoparticles offer neuroprotection to adult rat spinal cord neurons. , 2007, Biomaterials.

[24]  B. Lundqvist,et al.  Quantum origin of the oxygen storage capability of ceria. , 2002, Physical review letters.

[25]  Robert N Grass,et al.  In vitro cytotoxicity of oxide nanoparticles: comparison to asbestos, silica, and the effect of particle solubility. , 2006, Environmental science & technology.

[26]  A. Ghahary,et al.  Human dermal fibroblasts produce nitric oxide and express both constitutive and inducible nitric oxide synthase isoforms. , 1996, The Journal of investigative dermatology.

[27]  G. Duménil,et al.  Genotoxic activity of potassium permanganate in acidic solutions. , 1991, Mutation research.

[28]  R. Tice,et al.  A simple technique for quantitation of low levels of DNA damage in individual cells. , 1988, Experimental cell research.

[29]  B. Freeman,et al.  Microtubule dysfunction by posttranslational nitrotyrosination of alpha-tubulin: a nitric oxide-dependent mechanism of cellular injury. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[30]  K. Greulich,et al.  The distribution of the tail moments in single cell gel electrophoresis (comet assay) obeys a chi-square (chi2) not a gaussian distribution. , 1998, Mutation research.

[31]  Armand Masion,et al.  Enhanced adsorption of arsenic onto maghemites nanoparticles: As(III) as a probe of the surface structure and heterogeneity. , 2008, Langmuir : the ACS journal of surfaces and colloids.

[32]  Xiao-Dong Zhou,et al.  Toxicity of Cerium Oxide Nanoparticles in Human Lung Cancer Cells , 2006, International journal of toxicology.

[33]  A. Kasuya,et al.  Blue shift in ultraviolet absorption spectra of monodisperse CeO2−x nanoparticles , 2000 .

[34]  Robert N Grass,et al.  Oxide nanoparticle uptake in human lung fibroblasts: effects of particle size, agglomeration, and diffusion at low concentrations. , 2005, Environmental science & technology.

[35]  K. Jan,et al.  Ultrafine titanium dioxide particles in the absence of photoactivation can induce oxidative damage to human bronchial epithelial cells. , 2005, Toxicology.

[36]  F. Larachi,et al.  Ce 3d XPS study of composite CexMn1 xO2 y wet oxidation catalysts , 2002 .

[37]  G. Oberdörster,et al.  Nanotoxicology: An Emerging Discipline Evolving from Studies of Ultrafine Particles , 2005, Environmental health perspectives.

[38]  Suzette A. Morman,et al.  The Toxicological Geochemistry of Earth Materials: An Overview of Processes and the Interdisciplinary Methods Used to Understand Them , 2006 .

[39]  M. Fenech,et al.  Report from the In Vitro Micronucleus Assay Working Group , 2003, Mutation research.

[40]  D. Phillips Electron microscopy: use of transmission and scanning electron microscopy to study cells in culture. , 1998, Methods in cell biology.

[41]  Hiroshi Yamada,et al.  Investigation of a hepatotoxicity screening system in primary cell cultures --"what biomarkers would need to be addressed to estimate toxicity in conventional and new approaches?". , 2005, The Journal of toxicological sciences.

[42]  M. Fenech Cytokinesis-block micronucleus cytome assay , 2007, Nature Protocols.

[43]  Tetsuya Hoshino,et al.  Mechanism of polishing of SiO2 films by CeO2 particles , 2001 .

[44]  J. Chaudière,et al.  Intracellular antioxidants: from chemical to biochemical mechanisms. , 1999, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[45]  S. Seal,et al.  Fenton-like reaction catalyzed by the rare earth inner transition metal cerium. , 2008, Environmental science & technology.

[46]  D. Kittelson,et al.  The influence of a cerium additive on ultrafine diesel particle emissions and kinetics of oxidation , 2005 .