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Hussain et al. Particle and Fibre Toxicology 2010, 7:10 http://www.particleandfibretoxicology.com/content/7/1/10

RESEARCH
Research

Open Access

Carbon black and titanium dioxide nanoparticles elicit distinct apoptotic pathways in bronchial epithelial cells
Salik Hussain1,2, Leen CJ Thomassen3, Ioana Ferecatu1, Marie-Caroline Borot1, Karine Andreau1, Johan A Martens3, Jocelyne Fleury4,Armelle Baeza-Squiban1, Francelyne Marano1 and Sonja Boland*1

Abstract Background: Increasing environmental and occupational exposures to nanoparticles (NPs) warrant deeper insight into the toxicological mechanisms induced by these materials. The present study was designed to characterize the cell death induced by carbon black (CB) and titanium dioxide (TiO2) NPs in bronchial epithelial cells(16HBE14o- cell line and primary cells) and to investigate the implicated molecular pathways. Results: Detailed time course studies revealed that both CB (13 nm) and TiO2(15 nm) NP exposed cells exhibit typical morphological (decreased cell size, membrane blebbing, peripheral chromatin condensation, apoptotic body formation) and biochemical (caspase activation and DNA fragmentation) features ofapoptotic cell death. A decrease in mitochondrial membrane potential, activation of Bax and release of cytochrome c from mitochondria were only observed in case of CB NPs whereas lipid peroxidation, lysosomal membrane destabilization and cathepsin B release were observed during the apoptotic process induced by TiO2 NPs. Furthermore, ROS production was observed after exposure to CB and TiO2 buthydrogen peroxide (H2O2) production was only involved in apoptosis induction by CB NPs.
Conclusions: Both CB and TiO2 NPs induce apoptotic cell death in bronchial epithelial cells. CB NPs induce apoptosis by a ROS dependent mitochondrial pathway whereas TiO2 NPs induce cell death through lysosomal membrane destabilization and lipid peroxidation. Although the final outcome is similar (apoptosis), themolecular pathways activated by NPs differ depending upon the chemical nature of the NPs.

Background Nanotechnology industry is expanding at a rapid rate but in-depth exploration of the health and environmental effects of these materials is still warranted[1]. There is increasing evidence linking the NPs with human health problems. It has already been shown that inhaled carbonaceous NPs possessthe potential to aggravate existing respiratory disorders, such as asthma or bronchitis[2,3]. Translocation of NPs from the lungs towards other organs has been demonstrated and possible consequences include inflammation, heart rate and function anomalies, homeostatic disturbances and oxidative
* Correspondence: boland@univ-paris-diderot.fr
1 Université Paris Diderot - Paris 7, Unit of Functionaland Adaptive Biology (BFA)

CNRS EAC 4413, Laboratory of Molecular and Cellular Responses to Xenobiotics, 75205 Paris, France
Full list of author information is available at the end of the article

stress[4,5]. More recently it has also been shown that preinjected titanium dioxide nanoparticles can transform benign cells into aggressive metastatic tumor cells[6]. On the basis of currentknowledge, there is increasing need for the risk assessment of both CB and TiO2 due to increased environmental and occupational exposures. CB and TiO2 are among the most abundantly produced and widely utilized NPs. Major sources of CB NPs include combustion (considered as combustion derived ultrafine particles) and industry. These particles also represent the core of atmospheric pollution particles.TiO2 NPs are used in the preparation of sunscreens, cosmetics and tooth pastes[7,8]. Some recent estimates of annual global nano TiO2 production range between 5000-6400 metric tones[9,10]. These enormous amounts of nanomaterial

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