Table 2.
Summary of in vitro ligand activation of human and polar bear PXR by 51 pharmaceuticals and environmental pollutants. In vitro ligand activations in a COS-7-based luciferase reporter gene assay were expressed as maximum fold change of luciferase activity in lysates from exposed cells compared to the activity in DMSO control cells. Relative activation represents maximum responses as percentage of the maximum response resulting from activation of hPXR or pbPXR by rifampicin, while RECh20 represent the concentration required to induce a response equal to 20% of the maximum hPXR-mediated response induced by rifampicin. Students T-test was used to test for statistically significant differences in luciferase activities in exposed and DMSO-treated cells (*, p<0.05).
| Human PXR | Polar bear PXR | Relative max induction (polar bear vs human) | |||||
|---|---|---|---|---|---|---|---|
| Compound name | Fold induction | Relative activation (%) | RECh20 (M) | Fold induction | Relative activation (%) | RECh20 (M) | |
| Pharmaceuticals | |||||||
| Rifampicin | 9.8±0.9* | 100 % | 4.6E-7 | 7.4±1.5* | 76 % | 1.1E-6 | 0.8 |
| SR12813(1) | 7.0±1.1* | 72 % | 3.8E-8 | 9.4±0.9* | 96 % | 3.2E-7 | 1.3 |
| Carbamazepine | 2.3±0.3* | 23 % | 1.3E-5 | 1.4±0.3* | 14 % | N/D | 0.6 |
| Clotrimazole | 8.3±1.3* | 84 % | 3.4E-7 | 5.9±2.0* | 61 % | 6.3E-7 | 0.7 |
| Ketoconazole | 2.7±0.5* | 28 % | 1.3E-5 | 0.9±0.1 | 9 % | N/D | 0.3 |
| Omeprazole | 4.3±0.3* | 44 % | 9.1E-6 | 1.3±0.3 | 13 % | N/D | 0.3 |
| Pesticides | |||||||
| Methoxychlor | 7.3±0.7* | 75 % | 2.7E-6 | 3.9±0.5* | 40 % | 1.7E-5 | 0.5 |
| Dieldrin | 4.8±0.4* | 49 % | 1.7E-6 | 2.2±0.4* | 22 % | 2.5E-5 | 0.5 |
| Chlordane | 6.9±1.5* | 70 % | 1.7E-6 | 2.5±0.5* | 25 % | 1.6E-5 | 0.4 |
| Pentachlorophenol | 1.0±0.2 | 11 % | N/D | 0.9±0.3 | 9 % | N/D | 0.9 |
| Toxaphene | 4.6±0.3* | 47 % | 7.8E-7 | 7.0±0.8* | 71 % | 1.9E-6 | 1.5 |
| Endosulfan (α+β ~ 2:1) | 4.1±1.1* | 42 % | 7.8E-6 | 4.6±0.3* | 47 % | 4.5E-6 | 1.1 |
| α-hexachlorocyclohexane (α-HCH) | 5.6±1.5* | 57 % | 3.8E-6 | 1.3±0.8 | 13 % | N/D | 0.2 |
| Lindane (γ-HCH) | 9.3±0.6* | 94 % | 7.9E-7 | 9.0±2.9* | 92 % | 6.0E-6 | 1.0 |
| Vinclozolin | 3.7±0.2* | 38 % | 4.4E-5 | 1.1±0.2 | 11 % | N/D | 0.3 |
| 4,4′-DDT(2) | 5.2±0.6* | 53 % | 9.3E-6 | 4.1±0.6* | 42 % | 1.1E-5 | 0.8 |
| 4,4′-DDE(3) | 4.2±0.4* | 43 % | 9.1E-6 | 2.2±0.4* | 22 % | 3.6E-5 | 0.5 |
| 1,2,3-trichlorobenzene (1,2,3-TCB) | 0.9±0.1 | 9 % | N/D | 0.9±0.3 | 9 % | N/D | 0.9 |
| 1,2,4-trichlorobenzene (1,2,4-TCB) | 1.0±0.1 | 10 % | N/D | 0.9±0.3 | 9 % | N/D | 0.9 |
| Polychlorinated biphenyls | |||||||
| PCB 28 | 1.9±0.2* | 19 % | N/D | 1.1±0.1 | 12 % | N/D | 0.6 |
| PCB 47 | 2.6±0.1* | 27 % | 3.0E-5 | 1.4±0.4 | 14 % | N/D | 0.5 |
| PCB 52 | 1.1±0.2 | 11 % | N/D | 1.0±0.2 | 10 % | N/D | 0.9 |
| PCB 60 | 1.0±0.2 | 10 % | N/D | 0.8±0.1 | 8 % | N/D | 0.7 |
| PCB 97 | 2.4±0.4* | 25 % | 2.8E-5 | 2.7±0.6* | 28 % | 2.5E-5 | 1.1 |
| PCB 101 | 3.3±05* | 34 % | 2.0E-5 | 1.8±0.4* | 19 % | N/D | 0.6 |
| PCB 118 | 2.4±0.2* | 25 % | 3.4E-5 | 1.4±0.1* | 14 % | N/D | 0.6 |
| PCB 138 | 1.1±0.1 | 12 % | N/D | 1.1±0.1 | 11 % | N/D | 0.9 |
| PCB 151 | 7.1±1.0* | 72 % | 8.1E-6 | 1.5±0.2* | 15 % | N/D | 0.2 |
| PCB 153 | 3.2±0.3* | 33 % | 2.2E-5 | 3.0±0.2* | 31 % | 2.5E-5 | 0.9 |
| PCB 170 | 2.3±0.3* | 24 % | 3.5E-5 | 1.5±0.3* | 15 % | N/D | 0.6 |
| PCB 180 | 1.3±0.1* | 14 % | N/D | 1.6±0.3* | 16 % | N/D | 1.2 |
| PCB 183 | 2.9±0.5* | 28 % | 2.3E-5 | 3.0±0.6* | 31 % | 1.3E-5 | 1.1 |
| PCB 184 | 3.2±0.5* | 33 % | 5.4E-6 | 1.8±0.6* | 19 % | N/D | 0.6 |
| PCB 190 | 4.5±0.5* | 46 % | 9.8E-6 | 1.8±0.3* | 18 % | N/D | 0.4 |
| Brominated flame retardants | |||||||
| BDE 28 | 3.1±0.5* | 31 % | 1.1E-5 | 0.9±0.2 | 9 % | N/D | 0.3 |
| BDE 47 | 5.8±0.6* | 59 % | 5.0E-6 | 1.5±0.5* | 16 % | N/D | 0.3 |
| BDE 99 | 5.1±0.7* | 52 % | 4.8E-6 | 1.6±0.3* | 16 % | N/D | 0.3 |
| BDE 100 | 3.8±0.3* | 39 % | 6.6E-6 | 1.3±0.2* | 14 % | N/D | 0.4 |
| BDE 153 | 4.4±0.2* | 45 % | 3.9E-6 | 1.7±0.1* | 17 % | N/D | 0.4 |
| BDE 209 | 2.5±0.2* | 26 % | 1.6E-5 | 1.9±0.3* | 19 % | N/D | 0.7 |
| PentaBDE mix | 5.7±0.2* | 58 % | 5.1E-6 | 1.8±0.3* | 18 % | N/D | 0.3 |
| BDE47 (42%) | |||||||
| BDE99 (34%) | |||||||
| BDE100 (9%) | |||||||
| BDE153 (2%) | |||||||
| BDE154 (2%) | |||||||
| HBCD(4) technical mixture | 4.9±0.3* | 41 % | 2.6E-6 | 9.4±1.6* | 96 % | 1.7E-6 | 2.3 |
| α-HBCD (10%) | |||||||
| β-HBCD (9%) | |||||||
| γ-HBCD (81%) | |||||||
| Tetrabromobisphenol A (TBBPA) | 3.1±1.1* | 32 % | 2.9E-5 | 3.8±0.5* | 39 % | 3.5E-5 | 1.2 |
| Siloxanes | |||||||
| Hexamethylcyclotrisiloxane (D3) | 1.7±0.2* | 17 % | N/D | 1.1±0.2 | 11 % | N/D | 0.6 |
| Octamethylcyclotetrasiloxane (D4) | 4.3±0.3* | 44 % | 1.4E-5 | 1.1±0.4 | 11 % | N/D | 0.3 |
| Decamethylcyclopentasiloxane (D5) | 2.2±0.2* | 22 % | 3.5E-5 | 1.6±0.2* | 16 % | N/D | 0.7 |
| Miscellaneous | |||||||
| β-naphtoflavone (BNF) | 2.8±0.4* | 28 % | 6.9E-8 | 2.1±0.4* | 21 % | 6.9E-7 | 0.8 |
| 4-nonylphenol | 4.9±0.5* | 50 % | 1.9E-6 | 7.0±0.8* | 71 % | 4.8E-6 | 1.4 |
| 4-octylphenol | 1.7±0.2* | 17 % | N/D | 1.2±0.3 | 12 % | N/D | 0.7 |
| Bisphenol A (BPA) | 5.7±0.4* | 58 % | 6.6E-6 | 5.6±0.9* | 57 % | 2.1E-5 | 1.0 |
| Perfluorononanoic acid (PFNA) | 1.1±0.2 | 11 % | N/D | 0.9±0.3 | 10 % | N/D | 0.9 |
4-[2,2-bis(diethoxyphosphoryl)ethenyl]-2,6-ditert-butylphenol
Dichlorodiphenyltrichloroethane
Dichlorodiphenyldichloroethylene
Hexabromocyclododecane
* statistically significant difference between maximum luciferase activity induced via hPXR and pbPXR (T-test < 0.05)