Table 1 IC50 values (μM) of six test compounds obtained from the TeamChip.

From: High-throughput and combinatorial gene expression on a chip for metabolism-induced toxicology screening

Test compounds

Drug-metabolizing enzymes expressed in THLE-2 cells on the chip

 

No enzyme

CYP2C9

CYP2D6

CYP3A4

CYP1A2

Acetaminophen

1,400±250

930±41*

1,100±71

900±25*

820±21**

Bromfenac

190±12

120±6

170±39

260±24

190±37

Flutamide

37±9.7

25±4.8

27±5.1

24±1.6

18±0.5*

Tamoxifen

100±9.3

71±14

66±14*

100±7.1

120±3.5

Trifluoperazine

80±9.4

75±12

69±9.3

110±7.3

120±5.1

Troglitazone

92±6.4

50±4.9*

77±4.2

64±3.6*

39±6.6**

 

Drug-metabolizing enzymes expressed in THLE-2 cells on the chip

 

No enzyme

UGT1A4

P450 Mix

All Mix

Acetaminophen

1,500±63

2,100±52*

240±74**

640±100*

Bromfenac

210±17

210±14

220±24

260±5.5

Flutamide

45±1.6

38±1.8

18±4.1*

17±1.1**

Tamoxifen

93±18

180±14**

100±4.2

130±13

Trifluoperazine

75±11

100±12

53±13

110±10

Troglitazone

110±15

150±11*

51±4.3**

62±2.9*

  1. Errors are reported as average deviations (n=4).
  2. To determine statistically significant IC50 difference between no-enzyme control and enzyme test conditions, one-way ANOVA analysis was performed and the results were indicated as * for P<0.05 and ** for P<0.01. No indication means P>0.05.
  3. Fifteen MOI of individual recombinant adenoviruses were used for CYP2C9, CYP2D6, CYP3A4, CYP1A2, no enzyme and UGT1A4, and each three MOI of adenovirus mixtures were used for P450 Mix (CYP2C9, CYP2D6, CYP3A4, CYP1A2 and CYP2E1) and All Mix (CYP2C9, CYP2D6, CYP3A4, CYP1A2, CYP2E1 and UGT1A4).
  4. CYP2E1 (15 MOI) for acetaminophen resulted in IC50=180±50 μM. This gave P<0.01; one-way ANOVA versus no-enzyme control and versus all other CYP isoforms.
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