Table 3.
Impact of different synthetic cannabinoids on cytokinesis-block proliferation indices and on the rates of various nuclear aberrations in human mitogen-stimulated lymphocytes and in TR-146 cells
| Compounds | Concentration | CBPI | CT | BN–MNia | MNib | Nbuds | NPBs |
|---|---|---|---|---|---|---|---|
| µM | Mean ± SD | (%) | Mean (‰) ± SD | Mean (‰) ± SD | Mean (‰) ± SD | Mean (‰) ± SD | |
| Peripheral human lymphocytes | |||||||
| RCS-4 | 0 | 2.02 ± 0.14 | 0.0 | 4.14 ± 0.52 | 4.25 ± 0.49 | 2.96 ± 1.55 | 1.67 ± 0.75 |
| 25 | 1.79 ± 0.15 | 22.6 | 6.45 ± 1.24 | 6.92 ± 0.96 | 3.73 ± 1.36 | 2.72 ± 1.24 | |
| 50 | 1.52 ± 0.22* | 49.0 | 8.01 ± 0.7* | 8.46 ± 1.12* | 3.51 ± 1.05 | 2.98 ± 1.37 | |
| 75 | 1.25 ± 0.21* | 75.5 | n.e. | n.e | n.e. | n.e. | |
| 100 | 1.19 ± 0.17* | 81.4 | n.e. | n.e | n.e. | n.e. | |
| 150 | 1.07 ± 0.11* | 80.4 | n.e. | n.e | n.e. | n.e. | |
| XLR-11 | 25 | 1.86 ± 0.20 | 16.7 | 7.03 ± 1.76 | 7.26 ± 1.86 | 4.31 ± 1.95 | 1.81 ± 1.00 |
| 50 | 1.69 ± 0.22* | 32.4 | 6.04 ± 2.50 | 6.16 ± 2.70 | 3.13 ± 0.77 | 2.45 ± 0.88 | |
| 75 | 1.59 ± 0.14* | 43.1 | 8.54 ± 1.02 | 8.78 ± 1.02 | 4.48 ± 1.02 | 2.77 ± 0.66 | |
| 100 | 1.42 ± 0.13* | 58.8 | 14.51 ± 4.40* | 16.00 ± 5.71* | 9.08 ± 3.04* | 6.47 ± 3.02* | |
| 150 | 1.07 ± 0.05* | 93.1 | n.e. | n.e. | n.e. | n.e. | |
| Pos. Cont. | 1 µg/mL | 1.73 ± 0.16 | 48.36 ± 9.37* | 50.62 ± 10.10* | 12.44 ± 5.91* | 2.68 ± 1.16 | |
| Buccal-derived human cells (TR-146) | |||||||
| RCS-4 | 0 | 2.35 ± 0.44 | 1.39 ± 0.40 | 3.44 ± 0.34 | 1.34 ± 0.14 | 1.32 ± 0.34 | |
| 25 | 1.90 ± 0.75 | 33.3 | 3.46 ± 0.91 | 5.09 ± 1.09 | 3.92 ± 0.89 | 1.89 ± 0.97 | |
| 50 | 1.86 ± 0.32 | 36.3 | 4.67 ± 1.04 | 6.02 ± 1.02 | 3.35 ± 0.76 | 1.79 ± 0.50 | |
| 75 | 1.80 ± 0.25 | 40.7 | 6.89 ± 1.10* | 7.99 ± 0.90* | 3.92 ± 1.02 | 1.70 ± 0.40 | |
| 100 | 1.35 ± 0.86* | 74.1 | n. e. | n. e | n. e. | n. e | |
| 150 | 1.21 ± 0.45* | 84.4 | n. e. | n. e | n. e. | n. e | |
| XLR-11 | 25 | 1.99 ± 0.67 | 26.7 | 3.45 ± 0.97 | 5.20 ± 1.14 | 2.36 ± 0.89 | 1.12 ± 0.34 |
| 50 | 1.78 ± 0.14 | 42.2 | 4.49 ± 0.52 | 6.09 ± 1.00 | 2.42 ± 0.09 | 1.42 ± 0.88 | |
| 75 | 1.75 ± 0.43* | 44.4 | 6.46 ± 0.48* | 7.08 ± 1.34* | 2.99 ± 0.90 | 1.40 ± 0.36 | |
| 100 | 1.51 ± 0.54* | 62.2 | 8.98 ± 1.23* | 10.08 ± 2.10* | 2.32 ± 0.93 | 1.76 ± 0.78 | |
| 150 | 1.20 ± 0.13* | 85.2 | n. e. | n. e. | n. e. | n. e. | |
| Pos. Cont. | 1 µg/mL | 1.68 ± 0.09 | 45.21 ± 5.20* | 53.21 ± 7.60* | 10.34 ± 3.20* | 2.05 ± 1.06 | |
Human mitogen-stimulated lymphocytes from three individuals were treated with different concentrations of the test compounds for 3 h. TR-146 cells were exposed to different concentrations of the drugs for 24 h. Numbers represent results (means ± SDs) obtained with duplicate cultures from four donors. Per experimental point, two slides were prepared and 1000 cells were evaluated from each slide
n.e. not evaluated due to inhibition of cell division
Please exchange C+ to Pos. Cont. mitomycin C (1.0 μg/ml)
CBPI cytokinesis-block proliferation indices, CT cytostasis (%); BN–MNi binucleated cells with micronuclei, MNi total number of micronuclei, Nbuds nuclear buds, NPBs nucleoplasmic bridges, 0 solvent control (DMSO), C + mitomycin C (1.0 µg/mL)
* Significant differences from negative control (Kruskal–Wallis test followed by Dunns’s test, p ≤ 0.05)
aNumber of binucleated cell with micronuclei
bTotal number of MN