The authors found increased HDAC8 and decreased Rb1 expression in dioxin-treated AhR-wild type primary hepatocytes but not in those from AhR-null mice, demonstrating the role of AhR in determining HDAC8 over-expression and, consequently, the down-regulation of the tumor suppressor gene RB1. The modulation regulatory effect of RB1 by HDAC 8 was also determined by using hepatoma cells with ectopic HDAC 8 expression but transfected with AHR shRNAi. Here, AHR is linked to hepatocellular carcinoma.