ToxTracker Reporter Cell Lines as a Tool for Mechanism-Based (Geno)Toxicity Screening of Nanoparticles—Metals, Oxides and Quantum Dots
Abstract
:1. Introduction
2. Materials and Methods
2.1. Nanoparticles
2.2. Particle Morphology
2.3. Characterization of Particle Agglomeration
2.4. Cell Culture and Reagents
2.5. ToxTracker Assay (mES Cells)
2.6. Dose Metric Modelling Analysis
2.7. Statistical Analysis
3. Results
3.1. Particle Characterization
3.2. Nontoxic NPs—Several NPs Cause No Toxicity or ToxTracker Activation
3.3. Cytotoxicity—Several NPs and QDs Affect Cell Viability
3.4. Oxidative Stress—Many NPs and All QDs Induce Reporters Related to Oxidative Stress
3.5. DNA Damage—Few NPs Induce Reporters Related to DNA Damage
3.6. Protein Unfolding and p53 Related Stress—Few NPs and QDs Induce These Reporters
3.7. Dose Metric: Surface Area Appears to be the Most Suitable Dose Metric for CdTe QD Toxicity
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References and Notes
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Biological Damage | Cellular Pathway | Biomarker Gene |
---|---|---|
Oxidative stress | NRF2 antioxidant response | Srxn1 |
NRF2 independent | Blvrb | |
DNA damage | NF-kB signaling | Rtkn |
ATR/Chk1 DNA damage signaling | Bscl2 | |
Protein damage | Unfolded protein response | Ddit3 |
Cellular stress | P53 signaling | Btg2 |
Particle | Primary Size (TEM)/nm | Oxide Composition |
---|---|---|
Ag | Spherical, 5.2 ± 1.1 a | N/A |
Au | Spherical, 5.2 ± 0.9 a | N/A |
CdTe QDs | Spherical, 1.6, 2.6, 4.5, 6.5, 8.6 b | N/A |
Cr | Cubic and spherical, 10–115 | Cr */Cr2O3 |
Cr2O3 | Oval, 90–460 | Cr2O3 |
Mn | Spherical, 15–50 | Mn */MnO/MnO2/Mn2O3/Mn3O4 |
Mn3O4 | Cubic 20–180, rods 8000 × 400 | Mn3O4/MnO |
Pt | Spherical, 4.8 ± 0.8 a | N/A |
Sb | Irregular, 90–1200 | Sb */Sb2O3 |
Sb2O3 | Spherical, 70–250 | Sb2O3 |
Sn | Spherical, 20–250 | Sn */SnO/SnO2 |
SnO2 | Spherical, 2–3 (as aggregates) | SnO2 |
V | Rods 20 × 20 to 400 × 40 | V2O5/VO2 |
V2O5 | Irregular 40–450 | V2O5/VO2 |
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McCarrick, S.; Cappellini, F.; Kessler, A.; Moelijker, N.; Derr, R.; Hedberg, J.; Wold, S.; Blomberg, E.; Odnevall Wallinder, I.; Hendriks, G.; et al. ToxTracker Reporter Cell Lines as a Tool for Mechanism-Based (Geno)Toxicity Screening of Nanoparticles—Metals, Oxides and Quantum Dots. Nanomaterials 2020, 10, 110. https://doi.org/10.3390/nano10010110
McCarrick S, Cappellini F, Kessler A, Moelijker N, Derr R, Hedberg J, Wold S, Blomberg E, Odnevall Wallinder I, Hendriks G, et al. ToxTracker Reporter Cell Lines as a Tool for Mechanism-Based (Geno)Toxicity Screening of Nanoparticles—Metals, Oxides and Quantum Dots. Nanomaterials. 2020; 10(1):110. https://doi.org/10.3390/nano10010110
Chicago/Turabian StyleMcCarrick, Sarah, Francesca Cappellini, Amanda Kessler, Nynke Moelijker, Remco Derr, Jonas Hedberg, Susanna Wold, Eva Blomberg, Inger Odnevall Wallinder, Giel Hendriks, and et al. 2020. "ToxTracker Reporter Cell Lines as a Tool for Mechanism-Based (Geno)Toxicity Screening of Nanoparticles—Metals, Oxides and Quantum Dots" Nanomaterials 10, no. 1: 110. https://doi.org/10.3390/nano10010110