Table 2 Genotoxicity of TiO 2 NPs in vivo studies
From: Titanium dioxide nanoparticles: a review of current toxicological data
| Reference No. | Crystalline structure | Exposure mode | Concentration | Test type | Result |
|---|---|---|---|---|---|
| [21] | Anatase | HepG2 cells | 0, 1, 10, 100 and 250 μg/ml of TiO2 NPs | Comet assay | (+) |
| Fpg-Comet | (+) | ||||
| Upregulated mRNA expression (p53) | (+) | ||||
| Rutile | Comet assay | (±) | |||
| Fpg-Comet | (±) | ||||
| Upregulated mRNA expression (p53, mdm2, p21 and gadd45α) | (+) | ||||
| [28] | Anatase, 99.7% | A431 cells | 0.008 -80 μg/ml (10 times) | Comet assay | (+) |
| [30] | TiO2 NPs (99% pure) | Human lymph- oblastoid cells | 130 μg/ml | Cytokinesis-block micronucleus (CBMN) assays | (+) |
| HPRT mutation assay | (+) | ||||
| 65 μg/ml | Comet assay | (+) | |||
| [93] | Anatase/Rutile, 80/20 | NR8383 rat lung alveolar macrophages | 0, 10, 20, 40, 80 μg/cm2 | qRT-PCR (HO-1) | (+) |
| Immunocytochemistry (NF-κB) | (+) | ||||
| [114] | Rutile | CHO cells | 0,25, 50, 100 μg/ml | Mammalian chromosome aberration test | (+) |
| [155] | Spherical (anatase & rutile) | A549 cells | 100 μg/ml | Single strand breaks Comet assay | (+) |
| HPLC-MS/MS | (+) | ||||
| 8-oxodCuo | (+) | ||||
| [156] | P30.6 | WISH cells | 0.625-20 μg/ml | Olive tail moment | (+) |
| ROS generation | (+) | ||||
| Cell cycle arrest | (+) | ||||
| [157] | Anatase (< 100 nm) | IMR90 cells BEAS-2B cells | 0,2,5,10,50 μg/cm2 | Olive tail moment | (−) |
| DNA breaks | (−) | ||||
| [158] | V2O5 treated TiO2 anatase | V79 cells | 0,1,5,10,15,25 μg/cm2 | Micronucleus test | (+) |
| DNA damage | (+) | ||||
| Untreated anatase | |||||
| [159] | Spherical (anatase) Spicular (rutile) | THP-1 cells | 0,20, 100, 500 μg/ml | ROS | (+) |
| [160] | Anatase, 99% | U937 cells | 0.005-4 mg/ml | DNA fragmentation | (+) |
| [161] | Anatase/rutile, 80/20 | RAW264.7 cells | 0,1, 5, 10, 40 or 80 μg/cm2 | DNA fragmentation | (+) |
| ELISA (CDDE) | (−) | ||||
| [162] | P25 (70-85% Anatase, 30-15% rutile) | Human perip- heral blood lymphocytes | 0, 20, 50, 100 μg/ml | Flow cytometry of apoptosis | (+) |
| Western blot (cleaved caspase-8, -3, Bid, and cleaved PARP) | (+) | ||||
| SiRNA transfection | (+) | ||||
| [163] | Anatase | BEAS 2B cells | 0, 5, 50, 100 μg/ml | PCR (Caspase 3 and PARP) | (+) |
| SiRNA knockoutt Bid expression | (−) | ||||
| Western blot (bcl-2, bax, t-Bid, caspase 9, cytochrome C and p53) | (+) | ||||
| [164] | P-25 (70–85% Anatase, 30–15% rutile) | Human perip- heral blood lymphocytes | 0, 20, 50, 100 μg/ml | Comet assay | (+) |
| Western-blot(p53, p63, phospho-p53, Chk1, phospho-Chk1, Chk2, phospho-Chk2, phospho-FKHR, phospho-FKHRL1) | (+) | ||||
| [165] | P-25 (75% Anatase, 25% rutile) | HaCaT cells | 200 μg/ml | Flow cytometry of apoptosis | (+) |
| mRNA expression (Keratin 6) | (+) | ||||
| [166] | TiO2 NPs | Human lymphocytes | 0,2,4,6,8,10 mM | Comet assay | (+) |
| DNA ladder assay | (+) | ||||
| [167] | Rutile (>95%, <5% SiO2 coating) anatase (99.7%) | BEAS 2B cells | 1-100 μg/cm2 | Comet assay | (−) |
| CBMN assay | (−) | ||||
| Comet assay | (+) | ||||
| CBMN assay | (+) | ||||
| [168] | PEG-TiO2 NPs (P25 80% anatase, 20% rutile) | NCI-H292, HeLa and HepG2 cells | 75 μg/ml | RT-PCR (CSF-2) | (−) |
| RT-PCR (IL6, HMOX-1) | (+) | ||||
| [169] | Anatase, anatase/rutile | Caco-2 cells | 20, 80 μg/cm2 | Fpg-comet assay | (+) |
| [170] | Anatase (10/20) | BEAS-2B cells | 0, 5, 10 μg/ml | Micronucleus test | (+) |
| Comet assay | (+) | ||||
| [171] | P15 | NIH 3T3 cells and human fibroblast HFW cells | 10 μg/ml | Micronucleus assay | (+) |
| ROS | (+) | ||||
| 50 μg/ml | Colony forming assay | (+) | |||
| 0-100 μg/ml | Western blot (ERK, MEK) | (+) | |||
| [172] | Ultrafine (≤20 nm) | SHE cells | 0,0.5, 1, 5, 10 μg/cm2 | Micronucleus assay | (+) |
| Kinetochore staining | (+) | ||||
| DNA fragmentation | (+) | ||||
| DNA ladder assay | (−) | ||||
| [173] | P25 anatase | SHE cells | 0,10, 25, 50 μg/cm2 | Comet assay | (+) |
| [174] | TiO2 NPs | Chinese ham- ster ovary-K1 (CHO-K1) cells | 0.5, 1 μg/ml | Sister chromatid exchange (SCE) | (+) |
| Micronucleus assay | (+) | ||||
| [175] | Anatase (100% <25 nm) | Chinese ham- ster ovary-K1 (CHO-K1) cells | 0, 10, 20, 40 μg/ml | Comet assay | (−) |
| Gene mutation assay (Hprt) | (−) | ||||
| [176] | P25(99.5% purity, 73–85% anatase/14–17% rutile and 2–13% amorphous) | Human neonatal foreskin fibroblast cells | 0, 10, 25, 50, 100, 250, 500, 1000 μg/ml | DNA damage | (+) |
| Immunofluorescent (γ-H2AX) | (+) | ||||
| [177] | Anatase (15 nm, 100%) | Human dermal fibroblasts | 0, 1, 3, 10 μg/ml | DNA damage (ATM/Chk2) | (+) |
| [179] | P28 (anatase 90%, rutile 10%) | A549 cells | 0, 5, 15 μg/ml | ROS | (−) |
| DNA double strand breaks (γ-H2AX) | (−) | ||||
| [180] | P25 | A549 cells | 25-500 μg/ml | mRNA expression (Grp78 | (−) |
| and Hsp70) | |||||
| Western blot (Grp78 | (−) | ||||
| and Hsp70) | |||||
| [181] | TiO2 NPs | TA-100 cells | 200 μg/ml | Comet assay | (−) |
| [182] | P25, UV-titan M60 | Rat liver epithelial cells | 0, 5, 10, 20 μg/ml | Micronucleus assay | (−) |
| [183] | Surface treated rutile TiO2 | Caco-2 cells | 100 μg/ml | Gene expression analysis | (−) |