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1.
Toxicol In Vitro ; 27(1): 24-33, 2013 Feb.
Article in English | MEDLINE | ID: mdl-22985735

ABSTRACT

Due to unique surface chemistries and the ability to easily functionalize their surface, amorphous silica nanoparticles are being assimilated into medicinal and consumer products at an increasing rate. Subsequently, there is an emergent need to understand the interactions of these particulates with biological systems in an attempt to mitigate toxicity. The identification of susceptible or resistant cell types of the pulmonary system remains a critical step in the development of toxicity assessments for nanoparticle-based platforms. Specific to this study, the cellular responses of A549 lung epithelial and MeT-5A pleural mesothelial cell lines as a means of detecting nanoparticle-induced oxidative stress were examined. Basal expression and cellular antioxidant activity, including SOD, CAT, and GSH, were examined prior to H(2)O(2) and ~30 nm SiO(2) (0.01-100mg/L) exposures. Dose-response observations were made regarding oxidant production, cytotoxicity, GSH depletion and NRF2 transcription factor activation. Results indicated that, while both cell types exhibited susceptibility to H(2)O(2) and SiO(2)-induced oxidative stress and damage, the A549 cell line was relatively more resilient.


Subject(s)
Epithelial Cells/drug effects , Nanoparticles/toxicity , Silicon Dioxide/toxicity , Catalase/metabolism , Cell Line , Cell Line, Tumor , Cell Survival/drug effects , Epithelial Cells/metabolism , Epithelium , Glutathione/metabolism , Humans , Lung/cytology , NF-E2-Related Factor 2/metabolism , Superoxide Dismutase/metabolism
2.
Toxicol Lett ; 210(3): 293-301, 2012 May 05.
Article in English | MEDLINE | ID: mdl-22342292

ABSTRACT

There are many efforts in understanding the effects of nanoparticles on cell viability and metabolism, however, not much is known regarding the distinct molecular mechanisms of inflammation and cellular stress using low dosing concentrations. To address this gap in the literature, we utilized a novel experimental design that specifically probes the effects of a panel of commonly studied engineered nanomaterials along immunomodulatory pathways, including NF-κB. The panel of particles selected for this study included quantum dot nanocrystals, titanium dioxide, hydroxylated fullerenes, and silver nanoparticles. Cell viability, antioxidant activity, select messenger RNA, and protein modulation were studied in primary human dermal fibroblasts (HDF) and NF-κB knockdown HDF cells. Inflammatory and non-inflammatory immune responses were measured using protein and real-time PCR array analysis from HDF cells exposed to sub-lethal concentrations of nanoparticles. Differences in cellular response to nanoparticles in protein and antioxidant experiments were evident in NF-κB knockdown cells. The methods used in the study, along with the resultant data sets, serve as a potential model for studying the complex pathway-specific biochemical responses in cell and tissue systems associated with nanoparticle exposures.


Subject(s)
Fibroblasts/drug effects , Immunologic Factors/pharmacology , Metal Nanoparticles/toxicity , Silver/toxicity , Cell Survival/drug effects , Cells, Cultured , Extracellular Signal-Regulated MAP Kinases/metabolism , Glutathione/metabolism , Humans , NF-kappa B/physiology , Oxidation-Reduction
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