We first used a mouse hepatoma cell line stably expressing an AhR responsive luciferase reporter gene (Hepa1.1) [24] and found that leflunomide activated AhR transcription starting from 1 μM in a dose-dependent manner (Figure 1A), which was in accordance with our screening data and other published studies.[17] To further assess leflunomide activation of the AhR, we transiently transfected human HepG2 and mouse WT Hepa1 hepatoma cells with a luciferase reporter gene expression vector under control of a promoter containing xenobiotic response elements (XRE-Luc). This evidence concerns the gene AHR and hepatocellular carcinoma.