title: Toxicological assessment of multi-walled carbon nanotubes on A549 human lung epithelial cells.
abstract: An in vitro model resembling the respiratory epithelium was used to investigate the biological response to laboratory-made pristine and functionalised multi-walled carbon nanotubes (pMWCNT and MWCNT-COOH). Cell uptake was analysed by MWCNT-COOH, FITC labelled and the effect of internalisation was evaluated on the endocytic apparatus, mitochondrial compartment and DNA integrity. In the dose range 12.5-100μgml(-1), cytotoxicity and ROS generation were assayed, evaluating the role of iron (the catalyst used in MWCNTs synthesis). We observed a correlation between MWCNTs uptake and lysosomal dysfunction and an inverse relationship between these two parameters and cell viability (P<0.01). In particular, pristine-MWCNT caused a time- and dose-dependent ROS increase and higher levels of lipid hydroperoxides compared to the controls. Mitochondrial impairment was observed. Conversely to the functionalised MWCNT, higher micronuclei (MNi) frequency was detected in mono- and binucleate pMWCNT-treated cells, underlining an aneugenic effect due to mechanical damage. Based on the physical and chemical features of MWCNTs, several toxicological pathways could be activated in respiratory epithelium upon their inhalation. The biological impacts of nano-needles were imputable to their efficient and very fast uptake and to the resulting mechanical damages in cell compartments. Lysosomal dysfunction was able to trigger further toxic effects.
authors.affiliation: Department of Biomedical Sciences and Morphological and Functional Images, University of Messina, Italy.
authors.forename: Giuseppa
authors.initials: G
authors.lastname: Visalli
authors.affiliation: Department of Biomedical Sciences and Morphological and Functional Images, University of Messina, Italy.
authors.forename: Maria Paola
authors.initials: MP
authors.lastname: Bertuccio
authors.affiliation: Department of Electronic Engineering, Industrial Chemistry and Engineering, University of Messina, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Iannazzo
authors.affiliation: Department of Chemical Sciences, University of Messina, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Piperno
authors.affiliation: Department of Electronic Engineering, Industrial Chemistry and Engineering, University of Messina, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Pistone
authors.affiliation: Department of Biomedical Sciences and Morphological and Functional Images, University of Messina, Italy. Electronic address: adipietr@unime.it.
authors.forename: Angela
authors.initials: A
authors.lastname: Di Pietro
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D020552:Comet Assay; D003676:Deferoxamine / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007502:Iron Chelating Agents / Q000494:pharmacology; D008168:Lung / Q000166:cytology; D008247:Lysosomes / Q000378:metabolism; D015162:Micronucleus Tests; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D037742:Nanotubes, Carbon / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D007502:Iron Chelating Agents; D037742:Nanotubes, Carbon; D017382:Reactive Oxygen Species; D003676:Deferoxamine
keywords: Acid-treated multiwalled carbon nanotubes (MWCNT-COOH); Genotoxicity; Lysosomal and mitochondrial dysfunction; Oxidative damage; Pristine multi-walled carbon nanotubes (pMWCNT)