Bashir Mustafa Mohamed, Navin Kumar Verma, Adriele Prina-Mello, Yvonne Williams, Anthony M Davies, Gabor Bakos, Laragh Tormey, Connla Edwards, John Hanrahan, Anna Salvati, Iseult Lynch, Kenneth Dawson, Dermot Kelleher, and Yuri Volkov, Activation of stress-related signalling pathway in human cells upon SiO2 nanoparticles exposure as an early indicator of cytotoxicity, Journal of Nanobiotechnology, 9, 2011, 29-
Journal of Nanobiotechnology 9
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.
Please note: There is a known bug in some browsers that causes an
error when a user tries to view large pdf file within the browser window.
If you receive the message "The file is damaged and could not be
repaired", please try one of the solutions linked below based on the
browser you are using.
Items in TARA are protected by copyright, with all rights reserved, unless otherwise indicated.