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APAP induced biomarker expression (n=4) HepG2 cells

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Figure S2: Compound induced biomarker expression in HepG2 cells. The presented values (relative expression fold changes) represent mean values that were calculated from 3-5 independent experiments. The error bars illustrate the standard deviation of the independent experiments. A gene was considered to be up regulated when crossing the threshold line, which illustrates a significant increase of at least 2.5 fold change induction.

0 0.01

0.04 0.2 1 5 0 0.01

0.04 0.2 1 5 0 0.01

0.04 0.2 1 5 0 0.01

0.04 0.2 1 5 0 0.01

0.04 0.2 1 5 0 0.01

0.04 0.2 1 5 0 0.01

0.04 0.2 1 5 0

1 2 3 4 5 6

APAP induced biomarker expression (n=4) HepG2 cells

Fo ld c h a n ge 2 - Δ Δ C T

(2)

0 0.01

0.04 0.2 1 5 0 0.01

0.04 0.2 1 5 0 0.01

0.04 0.2 1 5 0 0.01

0.04 0.2 1 5 0 0.01

0.04 0.2 1 5 0 0.01

0.04 0.2 1 5 0 0.01

0.04 0.2 1 5 0

0.5 1 1.5 2 2.5 3

ASP induced biomarker expression (n=3) HepG2 cells

CYP1B1 CYP3A7 Tubb2b Fibin G6PD RGCC Fbxo32

Concentration [mM]

Fo ld c h a n ge 2 - Δ Δ C T

(3)

0 0.51 2.6

12.8 64

30000 0 0.51 2.6

12.8 64

30000 0 0.51 2.6

12.8 64

30000 0 0.51 2.6

12.8 64

30000 0 0.51 2.6

12.8 64

30000 0 0.51 2.6

12.8 64

30000 0 0.51 2.6

12.8 64 30000 0

0.5 1 1.5 2 2.5 3

BPR induced biomarker expression (n=3) HepG2 cells

Fo ld c h a n ge 2 - Δ Δ C T

(4)

0 1.6 8 40 200

1000 0

1.6 8 40 200

1000 0

1.6 8 40 200

1000 0

1.6 8 40 200

1000 0

1.6 8 40200

1000 0

1.6 8 40 200

1000 0

1.6 8 40 200 1000 0

2 4 6 8 10 12 14 16 18

CBZ induced biomarker expression (n=3) HepG2 cells

CYP1B1 CYP3A7 Tubb2b Fibin G6PD RGCC Fbxo32

Concentration [µM]

Fo ld c h a n ge 2 - Δ Δ C T

(5)

0 0 0.01

0.06

0.32 90 0 0

0.01 0.06

0.32 90 0 0

0.01 0.06

0.32 90 0 0

0.01 0.06

0.32 90 0 0

0.01 0.06

0.32 90 0 0

0.01 0.06

0.32 90 0 0

0.01 0.06

0.32 90 0

0.5 1 1.5 2 2.5 3 3.5 4 4.5

CHL induced biomarker expression (n=3) HepG2 cells

Fo ld c h a n ge 2 - Δ Δ C T

(6)
(7)

0 0.06

0.32 1.6 8

400 0

0.06

0.32 1.6 8

400 0

0.06

0.32 1.6 8

400 0

0.06

0.32 1.6 8

400 0

0.06

0.32 1.6 8

400 0

0.06

0.32 1.6 8

400 0

0.06

0.32 1.6 8 400 0

0.5 1 1.5 2 2.5 3 3.5 4 4.5 5

DFN induced biomarker expression (n=3) HepG2 cells

Fo ld c h a n ge 2 - Δ Δ C T

(8)

0 0.01

0.06 0.32 1.6

700 0

0.01 0.06

0.32 1.6

700 0

0.01 0.06

0.32 1.6

700 0

0.01 0.06

0.32 1.6

700 0

0.01 0.06

0.32 1.6

700 0

0.01 0.06

0.32 1.6

700 0

0.01 0.06

0.32 1.6 700 0

0.5 1 1.5 2 2.5 3

FAM induced biomarker expression (n=3) HepG2 cells

CYP1B1 CYP3A7 Tubb2b Fibin G6PD RGCC Fbxo32

Concentration [µM]

Fo ld c h a n ge 2 - Δ Δ C T

(9)

0 0.01

0.06

0.32 1.6 40 0 0.01

0.06

0.32 1.6 40 0 0.01

0.06

0.32 1.6 40 0 0.01

0.06

0.32 1.6 40 0 0.01

0.06

0.32 1.6 40 0 0.01

0.06

0.32 1.6 40 0 0.01

0.06

0.32 1.6 40 0

0.5 1 1.5 2 2.5 3 3.5 4 4.5 5

HYZ induced biomarker expression (n=4) HepG2 cells

Fo ld c h a n ge 2 - Δ Δ C T

(10)

0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5

INAH induced biomarker expression (n=4) HepG2 cells

CYP1B1 CYP3A7 Tubb2b Fibin G6PD RGCC Fbxo32

Concentration [mM]

Fo ld c h a n ge 2 - Δ Δ C T

(11)
(12)

0 0.06

0.32 1.6 8 40 0 0.06

0.32 1.6 8 40 0 0.06

0.32 1.6 8 40 0 0.06

0.32 1.6 8 40 0 0.06

0.32 1.6 8 40 0 0.06

0.32 1.6 8 40 0 0.06

0.32 1.6 8 40 0

0.5 1 1.5 2 2.5 3

LAB induced biomarker expression (n=3) HepG2 cells

CYP1B1 CYP3A7 Tubb2b Fibin G6PD RGCC Fbxo32

Concentration [µM]

Fo ld c h a n ge 2 - Δ Δ C T

(13)

0

0.32 1.6 8 40200 0

0.32 1.6 8 40 200 0

0.32 1.6 8 40 200 0

0.32 1.6 8 40 200 0

0.32 1.6 8 40 200 0

0.32 1.6 8 40200 0

0.32 1.6 8 40 200 0

0.5 1 1.5 2 2.5 3

LEV induced biomarker expression (n=3) HepG2 cells

Fo ld c h a n ge 2 - Δ Δ C T

(14)

0 0.02 0.1

0.51 2.6

100 0

0.02 0.1 0.51 2.6

100 0

0.02 0.1 0.51 2.6

100 0

0.02 0.1 0.51 2.6

100 0

0.02 0.1 0.51 2.6

100 0

0.02 0.1 0.51 2.6

100 0

0.02 0.1 0.51 2.6

100 0

0.5 1 1.5 2 2.5 3

MEL induced biomarker expression (n=3) HepG2 cells

CYP1B1 CYP3A7 Tubb2b Fibin G6PD RGCC Fbxo32

Concentration [nM]

Fo ld c h a n ge 2 - Δ Δ C T

(15)

0

0.32 1.6 8 40 200 0

0.32 1.6 8 40200 0

0.32 1.6 8 40 200 0

0.32 1.6 8 40 200 0

0.32 1.6 8 40 200 0

0.32 1.6 8 40 200 0

0.32 1.6 8 40 200 0

5 10 15 20 25 30 35 40 45 50

NFT induced biomarker expression (n=3) HepG2 cells

Fo ld c h a n ge 2 - Δ Δ C T

(16)

0

0.32 1.6 8 40 330 0

0.32 1.6 8 40330 0

0.32 1.6 8 40 330 0

0.32 1.6 8 40 330 0

0.32 1.6 8 40 330 0

0.32 1.6 8 40 330 0

0.32 1.6 8 40 330 0

2 4 6 8 10 12 14

NIM induced gene expression (n=3) HepG2 cells

CYP1B1 CYP3A7 Tubb2b Fibin G6PD RGCC Fbxo32

Concentration [µM]

Fo ld c h a n ge 2 - Δ Δ C T

(17)

0 1.6 8 40 200

1000 0

1.6 8 40 200

1000 0

1.6 8 40 200

1000 0

1.6 8 40 200

1000 0

1.6 8 40 200

1000 0

1.6 8 40 200

1000 0

1.6 8 40 200 1000 0

1 2 3 4 5 6 7 8

PhB induced biomarker expression (n=3) HepG2 cells

Fo ld c h a n ge 2 - Δ Δ C T

(18)

0 0.01

0.06

0.32 1.6 35 0 0.01

0.06

0.32 1.6 35 0 0.01

0.06

0.32 1.6 35 0 0.01

0.06

0.32 1.6 35 0 0.01

0.06

0.32 1.6 35 0 0.01

0.06

0.32 1.6 35 0 0.01

0.06

0.32 1.6 35 0

1 2 3 4 5 6

PMZ induced biomarker expression (n=3) HepG2 cells

CYP1B1 CYP3A7 Tubb2b Fibin G6PD RGCC Fbxo32

Concentration [µM]

Fo ld c h a n ge 2 - Δ Δ C T

(19)

0 1 2 3 4 5 6 7

PPL induced biomarker expression (n=3) HepG2 cells

Fo ld c h a n ge 2 - Δ Δ C T

(20)

0

0.32 1.6 8 40200 0

0.32 1.6 8 40 200 0

0.32 1.6 8 40 200 0

0.32 1.6 8 40 200 0

0.32 1.6 8 40 200 0

0.32 1.6 8 40200 0

0.32 1.6 8 40 200 0

0.5 1 1.5 2 2.5 3 3.5 4

RIF induced biomarker expression (n=3) HepG2 cells

CYP1B1 CYP3A7 Tubb2b Fibin G6PD RGCC Fbxo32 Baseline

Concentration [µM]

Fo ld c h a n ge 2 - Δ Δ C T

(21)

0 0.01

0.04 0.2 1 5 0 0.01

0.04 0.2 1 5 0 0.01

0.04 0.2 1 5 0 0.01

0.04 0.2 1 5 0 0.01

0.04 0.2 1 5 0 0.01

0.04 0.2 1 5 0 0.01

0.04 0.2 1 5 0

5 10 15 20 25

VPA induced biomarker expression (n=3) HepG2 cells

Fo ld c h a n ge 2 - Δ Δ C T

Abbildung

Figure  S2:    Compound  induced  biomarker  expression  in  HepG2  cells.  The  presented  values  (relative  expression  fold  changes) represent mean values that were calculated from 3-5 independent experiments

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