Table 2 Genotoxicity of TiO ₂ NPs in vivo studies

[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

(−)