Table 8.
Activation of liver injury modules in vitro and in vivo in rat hepatocytes after exposure to high- and low-risk liver toxicants. Bold text indicates significant activation of the Fibrosis module (p-value < 0.01).
| High-risk liver toxicants | |||||||
|---|---|---|---|---|---|---|---|
| Carbon tetrachloride | Lomustine | ||||||
| In vivo (DrugMatrix)a | In vivo (TG-GATEs)b | In vivo (DrugMatrix)c | In vitro (TG-GATEs)d | ||||
| Low-risk liver toxicants | |||||||
| Naproxen | Tamoxifen | ||||||
| In vivo (DrugMatrix)e | In vivo (TG-GATEs)f | In vivo (DrugMatrix)g | In vitro (TG-GATEs)h | ||||
| Anisonucleosis | 12.0 | Fibrosis | 4.5 | Fibrosis | 10.2 | Fibrosis | 2.9 |
| Fibrosis | 11.1 | Anisonucleosis | 4.4 | Cellular infiltration | 8.3 | Anisonucleosis | 2.4 |
| Cellular infiltration | 10.5 | Hematopoiesis | 3.7 | Cellular foci | 7.7 | Cellular infiltration | 2.2 |
| Cellular foci | 8.2 | Cellular foci | 2.8 | Single cell necrosis | 4.8 | Granular degeneration | 2.0 |
| Single cell necrosis | 5.9 | Cellular infiltration | 1.8 | Hematopoiesis | 4.5 | Oval cell proliferation | 1.9 |
| Nuclear alteration | 3.4 | Nuclear alteration | 1.7 | Anisonucleosis | 2.4 | Bile duct proliferation | 1.9 |
| Hematopoiesis | 2.2 | Granular degeneration | 1.7 | Bile duct proliferation | 2.2 | Hematopoiesis | 1.7 |
| Oval cell proliferation | 1.6 | Single cell necrosis | 1.3 | Oval cell proliferation | 2.0 | Cellular foci | 1.6 |
| Granular degeneration | 0.3 | Cytoplasmic alteration | 1.0 | Cytoplasmic alteration | 1.3 | Cytoplasmic alteration | 0.7 |
| Cytoplasmic alteration | -0.1 | Oval cell proliferation | 0.8 | Granular degeneration | 0.9 | Nuclear alteration | 0.1 |
| Bile duct proliferation | -0.3 | Bile duct proliferation | 0.7 | Nuclear alteration | 0.4 | Single cell necrosis | -0.2 |
| Nuclear alteration | 0.3 | Granular degeneration | 4.5 | Anisonucleosis | 3.4 | Anisonucleosis | 4.6 |
| Cytoplasmic alteration | 0.0 | Hematopoiesis | 2.4 | Granular degeneration | 1.8 | Hematopoiesis | 2.7 |
| Single cell necrosis | -0.3 | Cytoplasmic alteration | 1.9 | Cytoplasmic alteration | 1.1 | Fibrosis | 1.8 |
| Oval cell proliferation | -0.5 | Nuclear alteration | 1.9 | Nuclear alteration | 0.2 | Cytoplasmic alteration | 1.7 |
| Bile duct proliferation | -1.7 | Bile duct proliferation | 1.7 | Single cell necrosis | 0.1 | Granular degeneration | 1.6 |
| Anisonucleosis | -2.1 | Anisonucleosis | 1.5 | Fibrosis | -0.4 | Oval cell proliferation | 1.4 |
| Cellular foci | -2.4 | Oval cell proliferation | 1.2 | Cellular foci | -0.5 | Nuclear alteration | 1.4 |
| Cellular infiltration | -2.6 | Fibrosis | 1.1 | Cellular infiltration | -0.7 | Cellular infiltration | 1.0 |
| Granular degeneration | -2.6 | Single cell necrosis | 0.9 | Bile duct proliferation | -0.9 | Cellular foci | 0.8 |
| Fibrosis | -2.9 | Cellular foci | 0.8 | Hematopoiesis | -1.0 | Single cell necrosis | 0.1 |
| Hematopoiesis | -3.9 | Cellular infiltration | 0.1 | Oval cell proliferation | -1.0 | Bile duct proliferation | -0.1 |
aDose: 400 mg/kg; Time: 1, 3, 7, and 25 d. bDose: 1,000, 3,000, and 10,000 μM; Time: 2, 8, and 24 h. cDose: 4.2 and 8.75 mg/kg; Time: 1, 3, 5, and 25 d. dDose: 4.8, 24, and 120 μM; Time: 2, 8, and 24 h. eDose: 10 mg/kg; Time: 3 d. fDose: 80, 400, and 2000 μM; Time: 2, 8, and 24 h. gDose: 2.5 and 64 mg/kg; Time: 3 and 5 d. hDose: 0.12, 0.60, and 3.0 μM.