Proposed mechanism regulating the apoptotic pathway by PCBs in pituitary cells.

The non-dioxin-like PCB 180 increased apoptosis by activating the extrinsic pathway (TRADD, caspase-8). In contrast, the extrinsic (TRADD, caspase-8) and intrinsic (cytochrome c, caspase-9) pathways were down-regulated by the non-dioxin-like PCB 153, leading to an anti-apoptotic and putative proliferative phenotype. Changes in apoptosis by PCBs occur through the interference of PCB with TR, AhR and CYP1A1 action. A proposed mechanism is shown featuring the disruption of TR action by PCB 153 after its hydroxilation by CYP1A1, leading to an anti-apoptotic phenotype. In contrast, the disruption of AhR by PCB 180 led to a pro-apoptotic phenotype.