Project Summary (1997-1999)

The various toxic effects reported for polychlorinated biphenyl (PCB) commercial products include liver hypertrophy, neoplastic nodules and hepatocellular carcinoma. Many previous studies, that describe the potent promoting activities of numerous commercial PCB formulations and single congeners, have led to the general view that carcinogenicity of PCBs and related compounds is due to their activity as promoting agents. The mechanism of the promoting activity of PCBs, however, has not been determined. The main goal of this project, therefore, is to examine the mechanisms by which PCBs may exert their tumor-promoting activities. Investigators are examining the effect of PCBs on the induction of oxidative DNA damage in the form of 8-oxo-deoxyguanosine (8-oxo-dG); the effect of PCBs on cell proliferation and apoptosis in normal and preneoplastic hepatocytes; and the effect of PCBs on the activation of genes and transcription factors related to cell proliferation and apoptosis.