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Effect of a single dose of polychlorinated biphenyls on hepatic cell proliferation and the DNA binding activity of NF‐κB and AP‐1 in rats

Polychlorinated biphenyls (PCBs) are environmental pollutants that, because of their persistence and biomagnification, raise concerns about the health consequences of long‐term exposure. PCB mixtures induce hepatocellular carcinomas in rodents, but the mechanism of their promoting activity is not clear. Previous studies have shown that oxidative stress occurs after PCB administration, with the induction of lipid peroxidation and oxidative DNA damage, which may contribute to their promoting activity. In this study, we examined whether the oxidative stress‐sensitive transcription factors NF‐κB or AP‐1 were activated by PCBs in the liver. Male Sprague‐Dawley rats were injected i.p. with corn oil, 2,2′,4,4′,5,5′‐hexachlorobiphenyl (PCB‐153, 30, 150, or 300 μmol/kg), 3,3′,4,4′‐tetrachlorobiphenyl (PCB‐77, 30, 150, or 300 μmol/kg), or both PCBs (each 30 or 150 μmol/kg). Rats were euthanized 2, 6, or 24 h, or 2, 6, and 10 d after the PCB injection. Electrophoretic mobility shift assays (EMSAs) were performed to determine NF‐κB and AP‐1 DNA binding activities. The highest NF‐κB DNA binding activity was observed in rats receiving higher doses of PCB‐153 (150 and 300 μmol/kg), with peak activation occurring 2 d after injection. AP‐1 activation was not detected at any timepoint. Hepatocyte proliferation, as measured by the labeling index, was increased only in groups receiving the highest dose of PCB‐153 or the combination of two PCBs (150 μmol/kg each) at day 2, and not by any other PCB treatment at any timepoint. These results show that PCB‐153, but not PCB‐77, can induce hepatocyte proliferation and hepatic NF‐κB activation after a single dose. © 2003 Wiley‐Liss, Inc.