DNA damage and alterations in expression of DNA damage responsive genes induced by TiO2 nanoparticles in human hepatoma HepG2 cells

Petković, Jana; Žegura, Bojana; Stevanović, Magdalena; Drnovšek, Nataša; Uskoković, Dragan; Novak, Saša; Filipič, Metka

doi:10.3109/17435390.2010.507316

2011

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Authors

Petković, Jana
Žegura, Bojana
Stevanović, Magdalena

Drnovšek, Nataša
Uskoković, Dragan

Novak, Saša
Filipič, Metka

Article (Accepted Version)

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Abstract

We investigated the genotoxic responses to two types of TiO2 nanoparticles (<25 nm anatase: TiO2-An, and <100 nm rutile: TiO2-Ru) in human hepatoma HepG2 cells. Under the applied exposure conditions the particles were agglomerated or aggregated with the size of agglomerates and aggregates in the micrometer range, and were not cytotoxic. TiO2-An, but not TiO2-Ru, caused a persistent increase in DNA strand breaks (comet assay) and oxidized purines (Fpg-comet). TiO2-An was a stronger inducer of intracellular reactive oxygen species (ROS) than TiO2-Ru. Both types of TiO2 nanoparticles transiently upregulated mRNA expression of p53 and its downstream regulated DNA damage responsive genes (mdm2, gadd45α, p21), providing additional evidence that TiO2 nanoparticles are genotoxic. The observed differences in responses of HepG2 cells to exposure to anatase and rutile TiO2 nanoparticles support the evidence that the toxic potential of TiO2 nanoparticles varies not only with particle size but also...

Keywords:

TiO2 nanoparticles / genotoxicity / oxidative DNA damage / gene expression / HepG2 cells

Source:
Nanotoxicology, 2011, 5, 3, 341-353

Publisher:

Oxon : Taylor & Francis

Projects:

Molecular designing of nanoparticles with controlled morphological and physicochemical characteristics and functional materials based on them (RS-45004)
Slovenian Research Agency: Program P1-0245

Note:

This is the peer reviewed version of the article: Petković, Jana, Bojana Žegura, Magdalena Stevanović, Nataša Drnovšek, Dragan Uskoković, Saša Novak, and Metka Filipić. “DNA Damage and Alterations in Expression of DNA Damage Responsive Genes Induced by TiO2 Nanoparticles in Human Hepatoma HepG2 Cells.” Nanotoxicology 5, no. 3 (2011): 341–53. http://dx.doi.org/10.3109/17435390.2010.507316

DOI: 10.3109/17435390.2010.507316

ISSN: 1743-5390 (Print); 1743-5404 (Online)

PubMed: 21067279

WoS: 000294225600005

Scopus: 2-s2.0-80052073187

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TY  - JOUR
AU  - Petković, Jana
AU  - Žegura, Bojana
AU  - Stevanović, Magdalena
AU  - Drnovšek, Nataša
AU  - Uskoković, Dragan
AU  - Novak, Saša
AU  - Filipič, Metka
PY  - 2011
UR  - http://dais.sanu.ac.rs/123456789/568
AB  - We investigated the genotoxic responses to two types of TiO2 nanoparticles (<25 nm anatase: TiO2-An, and <100 nm rutile: TiO2-Ru) in human hepatoma HepG2 cells. Under the applied exposure conditions the particles were agglomerated or aggregated with the size of agglomerates and aggregates in the micrometer range, and were not cytotoxic. TiO2-An, but not TiO2-Ru, caused a persistent increase in DNA strand breaks (comet assay) and oxidized purines (Fpg-comet). TiO2-An was a stronger inducer of intracellular reactive oxygen species (ROS) than TiO2-Ru. Both types of TiO2 nanoparticles transiently upregulated mRNA expression of p53 and its downstream regulated DNA damage responsive genes (mdm2, gadd45α, p21), providing additional evidence that TiO2 nanoparticles are genotoxic. The observed differences in responses of HepG2 cells to exposure to anatase and rutile TiO2 nanoparticles support the evidence that the toxic potential of TiO2 nanoparticles varies not only with particle size but also with crystalline structure.
PB  - Oxon : Taylor & Francis
T2  - Nanotoxicology
T1  - DNA damage and alterations in expression of DNA damage responsive genes induced by TiO2 nanoparticles in human hepatoma HepG2 cells
SP  - 341
EP  - 353
VL  - 5
IS  - 3
DO  - 10.3109/17435390.2010.507316
ER  -

@article{
author = "Petković, Jana and Žegura, Bojana and Stevanović, Magdalena and Drnovšek, Nataša and Uskoković, Dragan and Novak, Saša and Filipič, Metka",
year = "2011",
url = "http://dais.sanu.ac.rs/123456789/568",
abstract = "We investigated the genotoxic responses to two types of TiO2 nanoparticles (<25 nm anatase: TiO2-An, and <100 nm rutile: TiO2-Ru) in human hepatoma HepG2 cells. Under the applied exposure conditions the particles were agglomerated or aggregated with the size of agglomerates and aggregates in the micrometer range, and were not cytotoxic. TiO2-An, but not TiO2-Ru, caused a persistent increase in DNA strand breaks (comet assay) and oxidized purines (Fpg-comet). TiO2-An was a stronger inducer of intracellular reactive oxygen species (ROS) than TiO2-Ru. Both types of TiO2 nanoparticles transiently upregulated mRNA expression of p53 and its downstream regulated DNA damage responsive genes (mdm2, gadd45α, p21), providing additional evidence that TiO2 nanoparticles are genotoxic. The observed differences in responses of HepG2 cells to exposure to anatase and rutile TiO2 nanoparticles support the evidence that the toxic potential of TiO2 nanoparticles varies not only with particle size but also with crystalline structure.",
publisher = "Oxon : Taylor & Francis",
journal = "Nanotoxicology",
title = "DNA damage and alterations in expression of DNA damage responsive genes induced by TiO2 nanoparticles in human hepatoma HepG2 cells",
pages = "341-353",
volume = "5",
number = "3",
doi = "10.3109/17435390.2010.507316"
}

Petković J, Žegura B, Stevanović M, Drnovšek N, Uskoković D, Novak S, Filipič M. DNA damage and alterations in expression of DNA damage responsive genes induced by TiO2 nanoparticles in human hepatoma HepG2 cells. Nanotoxicology. 2011;5(3):341-353

Petković, J., Žegura, B., Stevanović, M., Drnovšek, N., Uskoković, D., Novak, S.,& Filipič, M. (2011). DNA damage and alterations in expression of DNA damage responsive genes induced by TiO2 nanoparticles in human hepatoma HepG2 cells.
NanotoxicologyOxon : Taylor & Francis., 5(3), 341-353. 
https://doi.org/10.3109/17435390.2010.507316

Petković Jana, Žegura Bojana, Stevanović Magdalena, Drnovšek Nataša, Uskoković Dragan, Novak Saša, Filipič Metka, "DNA damage and alterations in expression of DNA damage responsive genes induced by TiO2 nanoparticles in human hepatoma HepG2 cells" 5, no. 3 (2011):341-353,
https://doi.org/10.3109/17435390.2010.507316 .