Table 4 Genotoxicity studies on cobalt particles
From: Poorly soluble cobalt oxide particles trigger genotoxicity via multiple pathways
Type of cobalt particle and nominal size | Cell model | Assays performed, concentration and exposure length | Results | Ref. |
|---|---|---|---|---|
Co metal particles | ||||
CoP (3.4 nm) CoMP (2.2 μm) | Balb/3 T3 mouse fibroblasts, clone A31-1-1 | Colony forming efficiency (0.1–100 μM, 4–72 h) | Concentration- and time-dependent cytotoxicity | 18 |
H2DCFDA (1–100 μM, 4 h) | Increased intracellular ROS | |||
GSH (1–100 μM, 4 h) | Reduced total GSH content | |||
LPO (1–100 μM, 4 h) | Concentration-dependent LPO formation | |||
Morphological transformation +/- ascorbic acid (1–20 μM, 72 h) | Induction of type-III foci, significantly decreased in the presence of ascorbic acid | |||
CoP (20–500 nm) | Balb/3 T3 mouse fibroblasts, clone A31-1-1 | Colony forming efficiency (0.1–100 μM, 2–24–72 h) | Concentration-related cytotoxicity | 22 |
Morphological transformation (1–30 μM, 72 h) | Increase in Type-III foci formation | |||
CBMN (1–10 μM, 24 h) | Statistically significant induction of MN | |||
Comet assay (1–5 μM, 2 h) | Induction of DNA damage | |||
CoP (100–500 nm) | Human peripheral blood leukocytes (PBLs) | CBMN (10-6-10-5 μM, 24 h) | Increase in MN formation | 45 |
Comet assay (10-5-10-4 μM, 2 h) | Concentration-dependent DNA damage | |||
CoP (<50 nm) | Mouse embryonic fibroblasts MEF Ogg1+/+ MEF Ogg1-/- | Automated cell counting method (0.05–40 μg ml-1, 24–48 h) | Cytotoxicity observed at 48 h exposure | 46 |
Comet assay (0.05–1 μg ml-1, 24 h) | No DNA damage | |||
FPG-modified comet assay (0.05–1 μg ml-1, 24 h) | DNA damage in MEF Ogg1-/- cells | |||
CoP (20 nm) | Human lung epithelial cells (A549) | Alamar blue (2.5–40 μg ml-1, 24 h) | Significant cytotoxicity at > 20 μg ml-1 | 47 |
H2DCFDA (2.5–15 μg ml-1, 12 h) | Concentration-dependent increase in ROS generation | |||
8-OHdG +/- NAC pre-treatment (2.5–15 μg ml-1, 12–24 h) | Oxidative stress and damage but not when cells are pre-incubated with NAC | |||
Comet assay (5–15 μg ml-1, 12 h) | Concentration- and time-related increase in DNA damage | |||
γ-H2Ax foci (5–15 μg ml-1, 12 h) | Pre-incubation of cells with NAC attenuated the DNA damage | |||
CoP (4 μm) | Human peripheral blood mononucleated cells (PBMC) | CBMN (0.6–6 μg ml-1, 15 min) | Statistically significant concentration-dependent increase in MN | 48 |
Comet assay (0.6–6 μg ml-1, 15 min) | No DNA damage | |||
Co3O4 particles | ||||
Commercially available Co3O4P Sigma- Aldrich (22 nm) | Human lung epithelial cells (A549) | LDH and WST-1 (1–40 μg ml-1, 0.5–2–24 h) | No cytotoxicity | 30 |
Comet assay (1–40 μg ml-1, 2–24 h) | DNA damage at the highest concentrations (20–40 μg ml-1) | |||
FPG-modified comet assay (1–40 μg ml-1, 2–24 h) | Oxidative DNA damage at the highest tested concentrations (20–40 μg ml-1) | |||
Human bronchial epithelial cells (BEAS-2B) | LDH (1–40 μg ml-1, 0.5–2–24 h) | Dose-related cytotoxicity only at 2 h exposure | ||
WST-1 (1–40 μg ml-1, 24 h) | Statistically significant viability reduction only at 40 μg ml-1 | |||
Comet assay (1–40 μg ml-1, 2–24 h) | Concentration-related DNA damage only at 40 μg ml-1 | |||
FPG-modified comet assay (1–40 μg ml-1, 2–24 h) | Oxidative DNA damage | |||
Commercially available Co3O4P, Sigma-Aldrich (264 nm by DLS; 22 nm by TEM) | Human hepatocarcinoma (HepG2) cells | LDH and MTT (5–40 μg ml-1, 24–48 h) | Concentration- and time-dependent cytotoxicity | 43 |
GSH/LPO/SOD/catalase (5–10–15 μg ml-1, 24–48 h) | Concentration- and time-related depletion of GSH and induction of LPO, SOD, and catalase | |||
Caspase-3 (5–10–15 μg ml-1, 24–48 h) | Concentration- and time-dependent increase of caspase-3 activity | |||
Comet assay | Concentration- and time-dependent DNA damage | |||