Activation of stress-related signalling pathway in human cells upon SiO2 nanoparticles exposure as an early indicator of cytotoxicity

Hdl Handle:
http://hdl.handle.net/10147/141550
Title:
Activation of stress-related signalling pathway in human cells upon SiO2 nanoparticles exposure as an early indicator of cytotoxicity
Authors:
Mohamed, Bashir M; Verma, Navin K; Prina-Mello, Adriele; Williams, Yvonne; Davies, Anthony M; Bakos, Gabor; Tormey, Laragh; Edwards, Connla; Hanrahan, John; Salvati, Anna; Lynch, Iseult; Dawson, Kenneth; Kelleher, Dermot; Volkov, Yuri
Citation:
Journal of Nanobiotechnology. 2011 Jul 29;9(1):29
Issue Date:
29-Jul-2011
URI:
http://hdl.handle.net/10147/141550
Abstract:
Abstract Background Nanomaterials such as SiO2 nanoparticles (SiO2NP) are finding increasing applications in the biomedical and biotechnological fields such as disease diagnostics, imaging, drug delivery, food, cosmetics and biosensors development. Thus, a mechanistic and systematic evaluation of the potential biological and toxic effects of SiO2NP becomes crucial in order to assess their complete safe applicability limits. Results In this study, human monocytic leukemia cell line THP-1 and human alveolar epithelial cell line A549 were exposed to a range of amorphous SiO2NP of various sizes and concentrations (0.01, 0.1 and 0.5 mg/ml). Key biological indicators of cellular functions including cell population density, cellular morphology, membrane permeability, lysosomal mass/pH and activation of transcription factor-2 (ATF-2) were evaluated utilizing quantitative high content screening (HCS) approach and biochemical techniques. Despite the use of extremely high nanoparticle concentrations, our findings showed a low degree of cytotoxicity within the panel of SiO2NP investigated. However, at these concentrations, we observed the onset of stress-related cellular response induced by SiO2NP. Interestingly, cells exposed to alumina-coated SiO2NP showed low level, and in some cases complete absence, of stress response and this was consistent up to the highest dose of 0.5 mg/ml. Conclusions The present study demonstrates and highlights the importance of subtle biological changes downstream of primary membrane and endocytosis-associated phenomena resulting from high dose SiO2NP exposure. Increased activation of transcription factors, such as ATF-2, was quantitatively assessed as a function of i) human cell line specific stress-response, ii) SiO2NP size and iii) concentration. Despite the low level of cytotoxicity detected for the amorphous SiO2NP investigated, these findings prompt an in-depth focus for future SiO2NP-cell/tissue investigations based on the combined analysis of more subtle signalling pathways associated with accumulation mechanisms, which is essential for establishing the bio-safety of existing and new nanomaterials.
Item Type:
Journal Article

Full metadata record

DC FieldValue Language
dc.contributor.authorMohamed, Bashir M-
dc.contributor.authorVerma, Navin K-
dc.contributor.authorPrina-Mello, Adriele-
dc.contributor.authorWilliams, Yvonne-
dc.contributor.authorDavies, Anthony M-
dc.contributor.authorBakos, Gabor-
dc.contributor.authorTormey, Laragh-
dc.contributor.authorEdwards, Connla-
dc.contributor.authorHanrahan, John-
dc.contributor.authorSalvati, Anna-
dc.contributor.authorLynch, Iseult-
dc.contributor.authorDawson, Kenneth-
dc.contributor.authorKelleher, Dermot-
dc.contributor.authorVolkov, Yuri-
dc.date.accessioned2011-09-02T08:11:10Z-
dc.date.available2011-09-02T08:11:10Z-
dc.date.issued2011-07-29-
dc.identifierhttp://dx.doi.org/10.1186/1477-3155-9-29-
dc.identifier.citationJournal of Nanobiotechnology. 2011 Jul 29;9(1):29-
dc.identifier.urihttp://hdl.handle.net/10147/141550-
dc.description.abstractAbstract Background Nanomaterials such as SiO2 nanoparticles (SiO2NP) are finding increasing applications in the biomedical and biotechnological fields such as disease diagnostics, imaging, drug delivery, food, cosmetics and biosensors development. Thus, a mechanistic and systematic evaluation of the potential biological and toxic effects of SiO2NP becomes crucial in order to assess their complete safe applicability limits. Results In this study, human monocytic leukemia cell line THP-1 and human alveolar epithelial cell line A549 were exposed to a range of amorphous SiO2NP of various sizes and concentrations (0.01, 0.1 and 0.5 mg/ml). Key biological indicators of cellular functions including cell population density, cellular morphology, membrane permeability, lysosomal mass/pH and activation of transcription factor-2 (ATF-2) were evaluated utilizing quantitative high content screening (HCS) approach and biochemical techniques. Despite the use of extremely high nanoparticle concentrations, our findings showed a low degree of cytotoxicity within the panel of SiO2NP investigated. However, at these concentrations, we observed the onset of stress-related cellular response induced by SiO2NP. Interestingly, cells exposed to alumina-coated SiO2NP showed low level, and in some cases complete absence, of stress response and this was consistent up to the highest dose of 0.5 mg/ml. Conclusions The present study demonstrates and highlights the importance of subtle biological changes downstream of primary membrane and endocytosis-associated phenomena resulting from high dose SiO2NP exposure. Increased activation of transcription factors, such as ATF-2, was quantitatively assessed as a function of i) human cell line specific stress-response, ii) SiO2NP size and iii) concentration. Despite the low level of cytotoxicity detected for the amorphous SiO2NP investigated, these findings prompt an in-depth focus for future SiO2NP-cell/tissue investigations based on the combined analysis of more subtle signalling pathways associated with accumulation mechanisms, which is essential for establishing the bio-safety of existing and new nanomaterials.-
dc.titleActivation of stress-related signalling pathway in human cells upon SiO2 nanoparticles exposure as an early indicator of cytotoxicity-
dc.typeJournal Article-
dc.language.rfc3066en-
dc.rights.holderMohamed et al.; licensee BioMed Central Ltd.-
dc.description.statusPeer Reviewed-
dc.date.updated2011-09-01T16:03:10Z-
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