Characterization of in vitro genotoxic, cytotoxic and transcriptomic responses following exposures to amorphous silica of different sizes
Bibliographic record
Abstract
• Genotoxic, cytotoxic and transcriptomic responses to silica particles were assessed. • Cellular responses to 12, 5–10 and 10–20 nm silica were compared to 2 μm silica. • Loss of cellular viability and enhanced micronuclei formation was size-dependent. • The toxicity did not correlate with the increases in the ROS levels. • Higher uptake and inability to clear 12 nm silica may explain their toxic potency. The objectives of the present study were to investigate the underlying mechanisms of genetic and cellular toxicity induced by silica nanoparticles (SiNPs) and determine if such toxicity is influenced by particle size. Commercially available amorphous SiNPs (12 nm, 5–10 nm, and 10–15 nm) and micrometer sized (SiP2 μm) silica were characterised for size, chemical composition, and aggregation state. Mouse lung epithelial (FE1) cells derived from Muta™Mouse were exposed to various concentrations (12.5, 25, 50, 100 μg/ml) of SiNPs and SiP2 μm. Cellular viability, clonogenic potential, oxidative stress, micronucleus formation, and mutant frequency were measured at different post-exposure time points. Cellular internalization of particles was assessed using nanoscale hyperspectral microscopy. Biological pathway and functional perturbations were assessed using DNA microarrays. Detailed characterization of particles confirmed their size, purity, and uniform dispersion in the exposure medium. Decreased cellular viability was observed acutely at 24 h at concentrations higher than 25 μg/ml for all particle types, with SiNPs being the most sensitive; loss of viability was surface area dependent at the lowest concentration tested. However, only SiNP12 showed poor long-term survival. A size-dependent increase in micronucleus formation was also observed for SiNPs. In contrast to the viability results, SiP2 μm exhibited the highest potential to induce oxidative stress compared to the SiNPs at all tested concentrations. Gene ontology and biological pathway analysis revealed significant changes in the expression of genes implicated in lysosomal functions in SiNP12-treated cells, which appear closely associated with higher SiNP12 internalization and lysosomal rearrangements in the cytoplasm of these cells. These results suggest that SiNPs induce cellular and genetic toxicity in a size-dependent manner and that the observed toxicity may be the results of higher particle internalization of smaller SiNP and subsequent lysosomal overload.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".