Comparison of Genotoxicity and Pulmonary Toxicity Study of Modified SiO2 Nanomaterials
Abstract
:1. Introduction
2. Materials and Methods
2.1. Samples
2.2. Animals
2.3. In Vitro Genotoxicity Study
2.3.1. Ames Test
2.3.2. Chromosomal Aberration (CA) Test
2.4. In Vivo Genotoxicity and Acute Pulmonary Toxicity Test
2.4.1. Acute Pulmonary Toxicity Test (1 D)
2.4.2. Rat Peripheral Blood Micronucleus Test and Acute Pulmonary Toxicity Test (14 D)
2.5. Statistical Analysis
3. Results
3.1. Ames Test
3.2. CA Test
3.3. MN Test
3.4. Acute Pulmonary Toxicity Test (1 D)
3.5. Acute Pulmonary Toxicity Test (14 D)
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Sample | Principal Component | Solid Content (%) | Diameter (nm) | pH |
---|---|---|---|---|
Sample A | Colloidal SiO2 | 41.13 | 55.16 | 7~9 |
Modified sample A | Sample A TEOS a H3FSi | 3.77 | 82.29 | 2~4 |
Sample B | Colloidal SiO2 | 35.8 | 22 | 7~9 |
Modified sample B | Sample B TEOS a H3FSi | 3.77 | 86.64 | 2~4 |
Group Code | Substance | Dose | Animal Number | |
---|---|---|---|---|
(mg/kg) | (mL/kg) | |||
NC 1 | R.D.W. | - | 0.5, i.t. | 6 |
SA | 80× diluted SA | 2.58 | 0.5, i.t. | 6 |
mSAH | 80× diluted mSA | 0.24 | 0.5, i.t. | 5 |
mSAL | 320× diluted mSA | 0.06 | 0.5, i.t. | 3 |
SB | 80× diluted SB | 2.24 | 0.5, i.t. | 6 |
mSB | 80× diluted mSB | 0.24 | 0.5, i.t. | 6 |
Group Code | Substance | Dose | Animal Number | |
---|---|---|---|---|
(mg/kg) | (mL/kg) | |||
NC 1 | R.D.W. | - | 0.5, i.t. | 5 |
PC | Cyclophosphamide | 20 | 10, i.p. | 4 |
SA | 320× diluted SA | 0.645 | 0.5, i.t. | 5 |
mSA | 320× diluted mSA | 0.06 | 0.5, i.t. | 5 |
SB | 80× diluted SB | 2.24 | 0.5, i.t. | 5 |
mSB | 80× diluted mSB | 0.24 | 0.5, i.t. | 5 |
Sample | SA | mSA | SB | mSB | |
Number of Revertants (Colony, CFU/Plate) | |||||
NC 1 | 22.7 ± 2.1 2 | 28.0 ± 5.1 | 25.0 ± 3.7 | 25.0 ± 3.7 | |
4NQO (positive control) | 213.7 ± 5.7 * | 586.3 ± 75.9 * | 468.3 ± 7.0 * | 468.3 ± 7.0 * | |
TA98/without S9 activation (mg/plate) | 0.0295 | - | 31.3 ± 0.9 | - | 20.7 ± 1.2 |
0.0589 | 22.0 ± 1.4 | 26.3 ± 5.4 | 25.0 ± 6.4 | 22.7 ± 3.1 | |
0.1178 | 20.3 ± 0.5 | 23.7 ± 1.7 | 23.0 ± 2.9 | 21.7 ± 2.5 | |
0.2356 | 23.0 ± 1.4 | 27.3 ± 1.2 | 21.0 ± 0.8 | 21.0 ± 2.2 | |
0.4713 | 23.7 ± 2.6 | 37.7 ± 3.7 | 25.3 ± 0.9 | 22.7 ± 1.2 | |
0.9425 | 22.7 ± 1.9 | - | 20.3 ± 0.5 | - | |
Sample | SA | mSA | SB | mSB | |
Number of Revertants (Colony, CFU/Plate) | |||||
NC | 27.3 ± 2.1 | 27.3 ± 2.1 | 34.0 ± 3.7 | 34.0 ± 3.7 | |
2-AA (positive control) | 2590.7 ± 138.9 * | 2590.7 ± 138.9 * | 1829.3 ± 236.1 * | 1829.3 ± 236.1 * | |
TA98/with S9 activation (mg/plate) | 0.0295 | - | 26.7 ± 2.5 | - | 34.7 ± 4.6 |
0.0589 | 28.7 ± 1.7 | 26.3 ± 3.1 | 33.3 ± 2.6 | 35.7 ± 0.9 | |
0.1178 | 31.3 ± 2.5 | 26.7 ± 3.4 | 34.0 ± 3.7 | 29.3 ± 1.2 | |
0.2356 | 27.7 ± 2.9 | 28.7 ± 3.4 | 35.0 ± 2.2 | 32.0 ± 2.2 | |
0.4713 | 26.0 ± 0.8 | 26.0 ± 3.7 | 31.7 ± 2.6 | 31.3 ± 4.2 | |
0.9425 | 27.7 ± 2.1 | - | 29.3 ± 2.6 | - |
Sample | SA | mSA | SB | mSB | |
Number of Revertants (Colony, CFU/Plate) | |||||
NC 1 | 194.7 ± 2.1 2 | 194.7 ± 2.1 | 143.0 ± 6.7 | 187.7 ± 7.8 | |
Sodium azide (positive control) | 1090.3 ± 52.1 * | 1090.3 ± 52.1 * | 1819.0 ± 196.5 * | 1665.3 ± 32.3 * | |
TA100/without S9 activation (mg/plate) | 0.0295 | 195.0 ± 10.7 | 188.3 ± 10.7 | - | - |
0.0589 | 188.0 ± 11.6 | 201.7 ± 15.5 | - | 182.3 ± 6.2 | |
0.1178 | 208.0 ± 11.4 | 195.7 ± 4.7 | 153.0 ± 7.8 | 192.3 ± 9.2 | |
0.2356 | 199.3 ± 7.0 | 184.7 ± 6.2 | 162.7 ± 10.6 | 189.0 ± 4.5 | |
0.4713 | 214.0 ± 13.4 | 204.7 ± 3.7 * | 225.0 ± 3.6 * | 172.7 ± 8.3 | |
0.9425 | - | - | 251.3 ± 13.5 * | 172.3 ± 2.1 | |
1.885 | - | - | 354.0 ± 5.9 * | - | |
Sample | SA | mSA | SB | mSB | |
Number of Revertants (Colony, CFU/Plate) | |||||
NC | 145.0 ± 10.6 | 145.0 ± 10.6 | 185.0 ± 8.3 | 185.0 ± 8.3 | |
2-AA (positive control) | 2449.3 ± 216.6 * | 2449.3 ± 216.6 * | 3288.3 ± 181.5 * | 3288.3 ± 181.5 * | |
TA100/with S9 activation (mg/plate) | 0.0295 | 135.3 ± 9.4 | 128.3 ± 6.9 | - | - |
0.0589 | 134.7 ± 7.7 | 130.0 ± 6.4 | - | 192.7 ± 9.3 | |
0.1178 | 128.7 ± 2.1 | 137.7 ± 10.3 | 168.7 ± 9.0 | 175.0 ± 5.7 | |
0.2356 | 136.7 ± 8.7 | 171.7 ± 9.5 | 192.3 ± 9.0 | 178.0 ± 7.5 | |
0.4713 | 129.0 ± 5.1 | 150.3 ± 8.7 | 182.3 ± 6.9 | 177.7 ± 5.2 | |
0.9425 | - | - | 193.0 ± 4.2 | 180.7 ± 7.1 | |
1.885 | - | - | 205.3 ± 9.0 | - |
Group | Dosage (mg/mL) | Frequency of Aberration (%) | Chromatic Type | Chromosome Type | |||
---|---|---|---|---|---|---|---|
Deletion | Intrachange | Interchange | Ring | Gap | |||
NC 1 | 0 | 2.7 ± 1.5 | 2.7 ± 1.5 | 0.0 ± 0.0 | 0.0 ± 0.0 | 0.0 ± 0.0 | 0.0 ± 0.0 |
Mitomycin C | 2.5 | 18.0 ± 2.6 * | 13.3 ± 6.1 * | 0.0 ± 0.0 | 3.3 ± 0.6 | 0.7 ± 0.6 | 5.0 ± 3.5 * |
SA | 1.387 | 2.3 ± 1.5 | 1.7 ± 0.6 | 0.0 ± 0.0 | 0.0 ± 0.0 | 0.0 ± 0.0 | 0.7 ± 1.2 |
mSA | 0.778 | 3.0 ± 2.0 | 2.7 ± 2.1 | 0.0 ± 0.0 | 0.0 ± 0.0 | 0.0 ± 0.0 | 0.3 ± 0.6 |
SB | 0.353 | 9.7 ± 1.5 *,a | 6.0 ± 2.0 a | 0.0 ± 0.0 | 0.7 ± 1.2 | 0.0 ± 0.0 | 4.0 ± 1.0 *,a |
mSB | 1.569 | 2.7 ± 1.5 a | 2.0 ± 1.0 a | 0.0 ± 0.0 | 0.0 ± 0.0 | 0.0 ± 0.0 | 0.7 ± 1.2 a |
Group | Dosage (mg/mL) | Frequency of Aberration (%) | Chromatic Type | Chromosome Type | |||
---|---|---|---|---|---|---|---|
Deletion | Intrachange | Interchange | Ring | Gap | |||
NC 1 | 0 | 2.7 ± 2.1 | 1.3 ± 1.2 | 0.0 ± 0.0 | 0.3 ± 0.6 | 0.0 ± 0.0 | 1.0 ± 1.0 |
Cyclophophamide | 25 | 12.7 ± 3.1 * | 13.7 ± 4.7 * | 0.0 ± 0.0 | 0.3 ± 0.6 | 0.0 ± 0.0 | 1.7 ± 0.6 |
SA | 1.387 | 3.3 ± 0.6 | 2.0 ± 0.0 | 0.0 ± 0.0 | 0.3 ± 0.6 | 0.3 ± 0.6 | 0.7 ± 0.6 |
mSA | 0.778 | 4.7 ± 2.1 | 2.3 ± 2.1 | 0.0 ± 0.0 | 0.0 ± 0.0 | 0.7 ± 0.6 | 2.0 ± 1.7 |
SB | 0.353 | 2.3 ± 0.6 | 2.0 ± 0.0 | 0.0 ± 0.0 | 0.3 ± 0.6 | 0.0 ± 0.0 | 0.0 ± 0.0 |
mSB | 1.569 | 3.3 ± 1.5 | 3.0 ± 2.0 | 0.0 ± 0.0 | 0.0 ± 0.0 | 0.0 ± 0.0 | 0.3 ± 0.6 |
Group/ Intervals | RETs/NCEs 1 (‰) | Mn-RETs/RETs (‰) |
---|---|---|
48 h | ||
NC 2 | 37.2 ± 7.4 3 | 8.1 ± 2.8 |
PC | 6.2 ± 1.9 * | 62.1 ± 36.5 * |
SA | 38.9 ± 7.0 | 7.5 ± 4.4 |
mSA | 35.7 ± 13.2 | 6.9 ± 4.5 |
SB | 25.7 ± 3.0 * | 12.4 ± 10.9 |
mSB | 28.1 ± 5.0 | 7.1 ± 4.6 |
72 h | ||
NC | 46.3 ± 8.2 | 4.6 ± 1.5 |
PC | 19.2 ± 4.9 * | 8.0 ± 2.7 * |
SA | 44.9 ± 6.6 | 4.2 ± 1.4 |
mSA | 38.4 ± 12.1 | 8.0 ± 4.1 |
SB | 34.9 ± 3.1 * | 8.8 ± 3.5 *,a |
mSB | 33.6 ± 4.6 * | 4.7 ± 1.3 a |
Group | Animal No. | Clinical Sign | Hours After Treatment | Mortality (%) 3 | ||
---|---|---|---|---|---|---|
1 | 12 | 24 | ||||
NC 1 | 6 | Normal | 0 2 | 0 | 0 | 0 |
SA | 6 | Normal | 0 | 0 | 0 | 0 |
mSAL | 5 | Normal | 0 | 0 | 0 | 0 |
SB | 6 | Normal | 0 | 0 | 0 | 0 |
mSB | 6 | Normal | 0 | 0 | 0 | 0 |
mSAH | 3 | Dyspnea | 0 | 1 | 1 | 66.6 |
Pathological Incidence | ||||||
Organ | Lesions | Group | ||||
NC 1 | SA | mSAL | SB | mSB | ||
Lung | ||||||
Edema, extensive | - | 4/6 | 2/5 | 3/6 | - | |
Hemorrhage, focal | - | - | 3/5 | 3/6 | 1/6 | |
Inflammation, alveolar, focal | - | 6/6 | 4/5 | 6/6 | 3/6 | |
Necrosis, alveolar wall, focal | - | 5/6 | 2/5 | 4/6 | - | |
Pathological Scores | ||||||
Organ | Lesions | Group | ||||
NC | SA | mSAL | SB | mSB | ||
Lung | ||||||
Edema, extensive | 0.0 ± 0.0 2,3 | 1.8 ± 1.5 * | 1.0 ± 1.4 | 2.0 ± 2.2 *,b | 0.0 ± 0.0 b | |
Hemorrhage, focal | 0.0 ± 0.0 | 0.0 ± 0.0 a | 1.2 ± 1.1*,a | 1.0 ± 1.1 * | 0.2 ± 0.4 | |
Inflammation, alveolar, focal | 0.0 ± 0.0 | 2.7 ± 0.8 * | 2.0 ± 1.6 * | 3.5 ± 1.2 *,b | 0.7 ± 0.8 b | |
Necrosis, alveolar wall, focal | 0.0 ± 0.0 | 2.2 ± 1.2 * | 1.0 ± 1.4 | 2.0 ± 1.7 *,b | 0.0 ± 0.0 b | |
Total score 4 | 0.0 ± 0.0 | 6.7 ± 3.2 * | 5.2 ± 5.2 * | 8.5 ± 5.5 *,b | 0.8 ± 1.2 b |
Group | WBC 2 (105) | E (105) | N (105) | L (105) | M (105) |
---|---|---|---|---|---|
NC 1 | 6.1 ± 2.9 3 | 0.0 ± 0.0 | 0.1 ± 0.1 | 0.3 ± 0.2 | 5.7 ± 2.7 |
SA | 23.7 ± 12.2 *,a | 0.4 ± 1.0 | 10.1 ± 8.1 * | 1.1 ± 0.7 * | 12.2 ± 3.9 * |
mSAL | 39.0 ± 10.8 *,a | 0.6 ± 0.7 | 20.4 ± 7.9 * | 2.0 ± 1.3 * | 16.1 ± 10.0 * |
SB | 33.5 ± 19.2 *,b | 0.4 ± 0.4 * | 15.6 ± 14.0 *,b | 2.2 ± 1.4 *,b | 15.3 ± 6.5 * |
mSB | 10.7 ± 10.7 b | 0.1 ± 0.2 | 0.8 ± 1.5 b | 0.5 ± 0.5 b | 9.4 ± 8.7 |
Pathological Incidence | ||||||
Organ | Lesions | Group | ||||
NC 1 | SA | mSA | SB | mSB | ||
Lung | ||||||
Aggregate of macrophage, alveolar multifocal | - | 4/5 2 | 5/5 | 5/5 | 0/5 | |
Granulomatous inflammation, alveolar, focal | - | - | - | 5/5 | 0/5 | |
Pathological Scores | ||||||
Organ | Lesions | Group | ||||
NC | SA | mSA | SB | mSB | ||
Lung, left lobe | ||||||
Aggregate of macrophage, alveolar multifocal | 0.0 ± 0.0 3,4 | 2.2 ± 1.5 * | 1.6 ± 0.5 * | 2.2 ± 0.4 *,a | 0.0 ± 0.0 a | |
Granulomatous inflammation, alveolar, focal | 0.0 ± 0.0 | 0.0 ± 0.0 | 0.0 ± 0.0 | 1.6 ± 0.5 *,a | 0.0 ± 0.0 a | |
Total score 5 | 0.0 ± 0.0 | 2.2 ± 1.5 * | 1.6 ± 0.5 * | 3.8 ± 0.8 *,a | 0.0 ± 0.0 a |
Group | M (105) | N (105) | L (105) | E (105) |
---|---|---|---|---|
NC 1 | 3.41 ± 0.88 2 | 0.03 ± 0.01 | 0.07 ± 0.05 | 0.00 ± 0.00 |
SA | 3.94 ± 0.49 | 0.18 ± 0.16 | 0.16 ± 0.08 | 0.01 ± 0.03 |
mSA | 7.28 ± 4.11 | 0.03 ± 0.03 | 0.19 ± 0.13 | 0.00 ± 0.00 |
SB | 5.09 ± 2.97 | 0.29 ± 0.24 * | 0.39 ± 0.41 | 0.00 ± 0.00 |
mSB | 3.97 ± 2.31 | 0.23 ± 0.34 | 0.16 ± 0.07 | 0.00 ± 0.00 |
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Chen, Y.-T.; Lue, P.-Y.; Chen, P.-W.; Chueh, P.-J.; Tsai, F.-J.; Liao, J.-W. Comparison of Genotoxicity and Pulmonary Toxicity Study of Modified SiO2 Nanomaterials. Appl. Sci. 2021, 11, 11990. https://doi.org/10.3390/app112411990
Chen Y-T, Lue P-Y, Chen P-W, Chueh P-J, Tsai F-J, Liao J-W. Comparison of Genotoxicity and Pulmonary Toxicity Study of Modified SiO2 Nanomaterials. Applied Sciences. 2021; 11(24):11990. https://doi.org/10.3390/app112411990
Chicago/Turabian StyleChen, Yng-Tay, Po-Yi Lue, Po-Wei Chen, Pin-Ju Chueh, Fuu-Jen Tsai, and Jiunn-Wang Liao. 2021. "Comparison of Genotoxicity and Pulmonary Toxicity Study of Modified SiO2 Nanomaterials" Applied Sciences 11, no. 24: 11990. https://doi.org/10.3390/app112411990
APA StyleChen, Y.-T., Lue, P.-Y., Chen, P.-W., Chueh, P.-J., Tsai, F.-J., & Liao, J.-W. (2021). Comparison of Genotoxicity and Pulmonary Toxicity Study of Modified SiO2 Nanomaterials. Applied Sciences, 11(24), 11990. https://doi.org/10.3390/app112411990