Table 4.
Induction of DNA migration in the human derived liver cell lines by different genotoxins
| Cell line | AFB1 | B(a)P | IQ | NDMA | PhIP | |||||
|---|---|---|---|---|---|---|---|---|---|---|
| Conc. (µM) | % DNA in tail | Conc. (µM) | % DNA in tail | Conc. (µM) | % DNA in tail | Conc. (mM) | % DNA in tail | Conc. (µM) | % DNA in tail | |
| HCC 1.2 | 0.0 1.0 5.0 20.0 |
1.38 ± 0.48 3.74 ± 2.69 4.02 ± 1.22 8.75 ± 1.48* |
0.0 2.0 10.0 50.0 |
0.68 ± 0.50 2.28 ± 1.77 3.07 ± 0.97 5.69 ± 2.10* |
0.0 25.0 50.0 100.0 |
2.93 ± 1.40 1.39 ± 0.94 1.86 ± 0.44 7.29 ± 1.87* |
0.0 50.0 100.0 200.0 |
1.77 ± 1.64 16.3 ± 4.52* 17.1 ± 3.64* 8.87 ± 0.30* |
0.0 50.0 100.0 300.0 |
6.61 ± 2.14 17.5 ± 4.84* 15.1 ± 2.32* 14.8 ± 2.63* |
| Hep3B | 0.0 1.0 5.0 20.0 |
0.93 ± 0.86 1.35 ± 0.81 4.03 ± 1.93* 4.31 ± 0.92* |
0.0 10.0 30.0 90.0 |
0.79 ± 0.66 3.97 ± 1.51* 2.47 ± 1.77 2.80 ± 1.30 |
0.0 50.0 100.0 250.0 |
0.92 ± 0.58 0.88 ± 0.71 1.75 ± 1.45 2.09 ± 1.38 |
0.0 50.0 100.0 200.0 |
0.57 ± 0.21 0.62 ± 0.45 0.92 ± 0.45 0.61 ± 0.47 |
0.0 25.0 50.0 100.0 |
1.56 ± 0.18 1.18 ± 0.39 1.43 ± 0.24 0.82 ± 0.53 |
| HepaRG | 0.0 5.0 10.0 20.0 |
4.16 ± 1.40 11.6 ± 1.50* 9.67 ± 2.17* 7.5 ± 1.76* |
0.0 2.0 10.0 50.0 |
1.43 ± 1.54 0.79 ± 0.36 5.72 ± 0.96* 6.71 ± 2.24* |
0.0 25.0 50.0 100.0 |
2.34 ± 2.92 3.34 ± 3.31 2.39 ± 4.10 2.38 ± 1.97 |
0.0 50.0 100.0 200.0 |
0.96 ± 0.59 1.47 ± 0.10 1.41 ± 1.04 5.09 ± 0.52* |
0.0 25.0 50.0 100.0 |
0.53 ± 0.66 2.56 ± 1.95 4.82 ± 3.57* 2.86 ± 1.73 |
| HepG2 | 0.0 1.0 5.0 20.0 |
1.02 ± 0.28 0.85 ± 0.41 2.96 ± 0.66* 5.17 ± 1.57* |
0.0 10.0 30.0 90.0 |
0.83 ± 0.62 14.3 ± 3.03* 15.4 ± 2.53* 13.5 ± 2.79* |
0.0 50.0 100.0 250.0 |
2.16 ± 0.54 1.32 ± 0.91 5.38 ± 2.02* 5.39 ± 1.94* |
0.0 50.0 100.0 200.0 |
0.35 ± 0.21 0.83 ± 0.26 1.12 ± 0.72 1.55 ± 0.49* |
0.0 25.0 50.0 100.0 |
2.90 ± 1.03 1.33 ± 0.83 6.92 ± 2.00* 6.78 ± 1.37* |
| HuH6 | 0.0 10.0 20.0 30.0 |
1.50 ± 1.09 3.35 ± 2.75 7.20 ± 3.1* 11.9 ± 4.30* |
0.0 10.0 30.0 90.0 |
0.91 ± 0.49 3.54 ± 0.88* 7.44 ± 1.58* 5.16 ± 1.91* |
0.0 25.0 50.0 100.0 |
4.01 ± 1.68 5.49 ± 2.24 5.91 ± 3.05 10.82 ± 5.71* |
0.0 50.0 100.0 200.0 |
1.73 ± 2.62 2.91 ± 1.45 6.86 ± 1.74* 13.1 ± 4.41* |
0.0 50.0 100.0 300.0 |
1.81 ± 1.15 11.51 ± 3.64* 8.67 ± 2.67* 24.7 ± 2.15* |
| HuH7 | 0.0 1.0 2.5 5.0 |
6.29 ± 1.57 2.76 ± 0.52 3.12 ± 0.70 5.81 ± 4.64 |
0.0 10.0 30.0 90.0 |
1.08 ± 0.47 2.00 ± 1.14 4.79 ± 1.25* 5.36 ± 1.03* |
0.0 50.0 100.0 250.0 |
1.29 ± 1.30 2.16 ± 0.91 1.11 ± 0.60 1.88 ± 1.68 |
0.0 50.0 100.0 200.0 |
0.61 ± 0.35 0.69 ± 0.48 0.77 ± 0.60 3.01 ± 2.11* |
0.0 50.0 100.0 300.0 |
5.12 ± 1.05 5.35 ± 2.84 9.21 ± 2.26 3.55 ± 2.08 |
| JHH6 | 0.0 1.0 2.5 5.0 |
1.67 ± 0.99 1.7 ± 0.75 n.d. 4.52 ± 1.43* |
0.0 10.0 50.0 90.0 |
1.67 ± 0.99 2.33 ± 1.18 3.78 ± 3.42 3.37 ± 1.96 |
0.0 25.0 50.0 100.0 |
0.59 ± 0.21 0.76 ± 0.56 1.29 ± 1.55 0.93 ± 0.67 |
0.0 50.0 100.0 200.0 |
1.17 ± 1.11 1.33 ± 0.66 1.69 ± 0.81 1.16 ± 0.53 |
0.0 25.0 50.0 100.0 |
0.59 ± 0.21 0.25 ± 0.15 0.93 ± 1.09 1.44 ± 0.53 |
| PLC/PRF | 0.0 1.0 2.5 5.0 |
1.84 ± 1.44 4.57 ± 1.83 4.77 ± 1.75 6.68 ± 2.94* |
0.0 10.0 30.0 90.0 |
1.09 ± 0.81 1.39 ± 0.55 1.31 ± 1.72 1.54 ± 0.87 |
0.0 50.0 100.0 250.0 |
2.47 ± 2.08 5.17 ± 4.50 2.84 ± 2.65 4.61 ± 1.54 |
0.0 50.0 100.0 200.0 |
1.15 ± 1.25 1.04 ± 0.33 1.65 ± 1.55 1.09 ± 0.33 |
0.0 50.0 100.0 300.0 |
3.82 ± 1.22 2.51 ± 0.56 4.00 ± 3.72 2.43 ± 2.03 |
| SK-Hep1 | 0.0 1.0 5.0 20.0 |
0.60 ± 0.41 1.30 ± 0.37 1.13 ± 0.72 1.24 ± 0.88 |
0.0 10.0 30.0 90.0 |
0.46 ± 0.29 0.87 ± 0.86 2.20 ± 2.36 1.17 ± 0.80 |
0.0 50.0 100.0 250.0 |
0.59 ± 0.24 0.62 ± 0.47 1.43 ± 0.95 0.68 ± 0.70 |
0.0 50.0 100.0 200.0 |
0.46 ± 0.16 0.70 ± 0.42 0.59 ± 0.24 0.37 ± 0.34 |
0.0 50.0 100.0 300.0 |
2.84 ± 2.06 5.18 ± 1.19 5.83 ± 1.06 5.77 ± 4.30 |
| SNU-398 | 0.0 1.0 5.0 10.0 |
2.50 ± 1.08 2.53 ± 1.68 3.06 ± 0.28 2.83 ± 0.61 |
0.0 10.0 30.0 90.0 |
0.64 ± 0.27 0.73 ± 0.45 0.56 ± 0.45 2.28 ± 2.73 |
0.0 50.0 100.0 250.0 |
1.02 ± 0.88 1.42 ± 0.72 1.20 ± 0.81 1.63 ± 1.25 |
0.0 50.0 100.0 200.0 |
0.40 ± 0.14 0.65 ± 0.50 0.83 ± 0.53 0.28 ± 0.11 |
0.0 50.0 100.0 300.0 |
5.60 ± 3.26 2.92 ± 1.18 7.04 ± 5.97 10.3 ± 1.06 |
| SNU-449 | 0.0 1.0 2.5 5.0 |
2.87 ± 2.05 2.04 ± 2.18 1.14 ± 1.95 3.37 ± 3.14 |
0.0 10.0 30.0 90.0 |
0.79 ± 0.41 1.26 ± 0.62 0.79 ± 0.21 0.74 ± 0.64 |
0.0 50.0 100.0 250.0 |
1.20 ± 1.18 3.67 ± 2.95 1.46 ± 1.21 0.18 ± 0.09 |
0.0 50.0 100.0 200.0 |
0.23 ± 0.16 0.52 ± 0.24 0.54 ± 0.11 0.15 ± 0.03 |
0.0 50.0 100.0 300.0 |
2.12 ± 0.59 2.02 ± 0.81 3.06 ± 1.08 1.17 ± 0.83 |
| WRL68 | 0.0 1.0 2.5 5.0 |
3.14 ± 1.66 2.32 ± 0.89 1.98 ± 0.41 1.72 ± 0.78 |
0.0 10.0 30.0 90.0 |
2.66 ± 1.17 3.10 ± 3.43 4.30 ± 0.34 6.10 ± 3.26 |
0.0 50.0 100.0 250.0 |
0.76 ± 0.77 1.15 ± 1.44 0.56 ± 0.67 1.32 ± 1.64 |
0.0 50.0 100.0 200.0 |
0.43 ± 0.22 1.03 ± 0.74 0.93 ± 0.05 0.12 ± 0.01 |
0.0 50.0 100.0 300.0 |
2.89 ± 1.16 5.17 ± 3.21 3.77 ± 1.36 3.39 ± 3.35 |
Numbers indicate means ± SD of results obtained in a representative experiment with two cultures per experimental point (100 cells were evaluated per culture). 25 µM H2O2 was included as a positive control in each experimental series, for experiments with HepaRG 50 µM were used. Significant positive results were obtained with H2O2 in all experiments (data not shown). Acute toxicity was determined in each experiment with the CASY® cell counter and analyzer system; the viability was in all experiments ≥ 70% (data not shown). Stars indicate statistical significance (Dunnett test; P value ≤ 0.05); n.d.: not determined