Project Summary (2000-2005)

The goal of this project is to test the hypothesis that certain transcription factors, such as NF-kB and AP-1, are important in the tumor promoting activity of PCBs. Researchers are examining mechanisms, such as increased oxidative stress, by which PCBs activate NF-kB and AP-1. The importance of hepatic Kupffer cells in the activation of NF-kB and AP-1, the induction of cell proliferation, and the promotion of preneoplastic lesions by PCBs are being studied. The consequences of NF-kB activation are being identified by analyzing downstream targets of these transcription factors after the administration of PCBs. Also, researchers are determining if the loss of the p50 subunit of NF-kB influences the promoting activity of PCBs. These studies show if NF-kB activation is necessary for the promoting activity of PCBs and are elucidating the mechanism by which NF-kB activation influences hepatic tumor promotion by PCBs.