Author/Editor		Petković, Jana; Žegura, Bojana; Filipič, Metka
Title		Influence of TiO2 nanoparticles on cellular antioxidant defense and its involvement in genotoxicity in HepG2 cells
Type		članek
Source		J Phys: Conf Ser
Vol. and No.		Letnik 304, št. 1
Publication year		2011
Volume		str. 1-8
Language		eng
Abstract		We investigated the effects of two types of TiO2 nanoparticles (<25 nm anatase, TiO2-An; <100 nm rutile, TiO2-Ru) on cellular antioxidant defense in HepG2 cells. We previously showed that in HepG2 cells, TiO2 nanoparticles are not toxic, although they induce oxidative DNA damage, production of intracellular reactive oxygen species, and up-regulation of mRNA expression of DNA-damage-responsive genes (p53, p21, gadd45? and mdm2). In the present study, we measured changes in mRNA expression of several antioxidant enzymes: catalase, superoxide dismutase, glutathione peroxidase, nitric oxide synthase, glutathione reductase and glutamate-cysteine ligase. As reduced glutathione has a central role in cellular antioxidant defense, we determined the effects of TiO2 nanoparticles on changes in the intracellular glutathione content. To confirm a role for glutathione in protection against TiO2-nanoparticle-induced DNA damage, we compared the extent of TiO2-nanoparticle-induced DNA damage in HepG2 cells that were glutathione depleted with buthionine-(S,R)-sulfoximine pretreatment and in nonglutathione-depleted cells. Our data show that both types of TiO2 nanoparticles up-regulate mRNA expression of oxidative-stress-related genes, with TiO2-Ru being a stronger inducer than TiO2-An. Both types of TiO2 nanoparticles also induce dose-dependent increases in intracellular glutathione levels, and in glutathione-depleted cells, TiO2-nanoparticle-induced DNA damage was significantly greater than in nonglutathione-depleted cells. Interestingly, the glutathione content and the extent of DNA damage were significantly higher in TiO2-An- than TiO2-Ru-exposed cells. Thus, we show that TiO2 nanoparticles cause activation of cellular antioxidant processes, and that intracellular glutathione has a critical role in defense against this TiO2-nanoparticle-induced DNA damage.
Descriptors		TUMOR CELLS, CULTURED TITANIUM OXIDES ANTIOXIDANTS DNA DAMAGE REACTIVE OXYGEN SPECIES MICROCHEMISTRY RNA, MESSENGER GLUTATHIONE POLYMERASE CHAIN REACTION