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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 (−)
  1. (+) positive; (−) negative; (±) uncertain.