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Research Brief 111Superfund Basic Research ProgramNutrition Can Modulate PCB ToxicityRelease Date: 03/03/2004 Although U.S. production of polychlorinated biphenyls (PCBs) was banned in the late 1970's, low levels of PCBs can still be found in almost all outdoor and indoor air, soil, sediments, surface water, and animals. Food consumption has been and continues to be the main contributor to body burden of PCBs in the general population, with fish, meat, and dairy products the main dietary sources. Dr. Bernhard Hennig at the University of Kentucky SBRP is leading a research program examining the interaction of diet and the cytotoxicity of environmental contaminants. His work focuses not on the PCB contaminant levels in food, but on the impacts that various components of the diet can have on the toxicity of PCBs. The Hennig laboratory has discovered that while some items in the diet can activate mechanisms leading to increased cellular dysfunction, others can protect against cell damage mediated by PCBs. The UK SBRP researchers investigated the mechanisms of PCB toxicity that result in dysfunction of vascular endothelial cells leading to cardiovascular diseases such as atherosclerosis. In a series of studies, the Hennig laboratory has gathered in vitro and in vivo evidence that coplanar PCBs (such as PCB 77, PCB 126 and PCB 169) disrupt endothelial function by increasing cellular oxidative stress. Coplanar PCBs interact with the aryl hydrocarbon receptor (AhR), resulting in activation of the cytochrome P450 1A (CYP1A1) subfamily of enzymes. One of the processes of induction of CYP1A1 is excessive generation of reactive oxygen species, leading to oxidative stress which can cause damage to DNA, proteins, lipids, and carbohydrates. Significantly, the UK researchers determined that PCB-induced oxidative stress is dose-dependent. Dr. Hennig's recent findings indicate that the interactions of coplanar PCBs with the AhR compromise the normal functions of vascular endothelial cells by activating oxidative stress-sensitive signaling pathways such as the transcription factor nuclear factor kappa-B (NF-kB) which in turn promote gene expression for inflammatory cytokines and adhesion molecules. These proinflammatory events are critical in the pathology of atherosclerosis and cardiovascular disease. However, non-coplanar PCBs also can induce activation of endothelial cells, leading to upregulation of a variety of chemokines and adhesion molecules which can be involved both in the development of atherosclerosis and cancer metastasis. Indeed, the UK researchers have evidence that PCB-induced endothelial responses lead to increased adhesion and migration of tumor cells across the in vitro models of vascular endothelium. In concert with these mechanistic studies, Dr. Hennig has examined the impact of dietary components on cellular responses to PCB exposure. This research has revealed that nutrients can modulate PCB-induced oxidative stress and endothelial toxicity. The UK scientists have demonstrated that the dietary fat linoleic acid, the parent unsaturated fatty acid of the omega-6 family, can increase endothelial dysfunction induced by coplanar PCBs, probably by contributing to oxidative stress and as the result of the production of toxic metabolites, including leukotoxins. Part of this work was performed in collaboration with Dr. Bruce Hammock's group from the UC Davis SBRP. Plant-derived oils such as corn oil and safflower oil are major sources of omega-6 unsaturated fatty acids - suggesting a similar role for these oils and complicating the development of appropriate advisories concerning plant oils vs. animal fats in the diet. Data from Hennig's laboratory also indicate that antioxidant nutrients such as vitamin E can protect against endothelial cell damage mediated by PCBs or polyunsaturated dietary fats by interfering with oxidative stress-sensitive and proinflammatory signaling pathways. Recently, Dr. Hennig tested the hypothesis that dietary flavonoids such as catechins (found in red wine and tea) and quercetin (found in fruits and vegetables) can modify PCB-mediated toxicity. These plant-derived biologically active compounds possess antioxidant and anti-inflammatory properties. The research revealed that both catechins and quercetin were able to block AhR activation by coplanar PCBs in a concentration-dependent manner. These findings suggest that these flavonoids may be of value for inhibiting the toxic effects of PCBs on vascular endothelial cells. The concept that nutrition may modify or ameliorate the toxicity of Superfund chemicals is provocative and warrants further study as the implications for human health are significant, especially for populations near sites of excessive exposure to environmental pollutants such as PCBs. The information from these studies could be used to develop dietary recommendations and nutritional interventions for populations at high risk for exposure to PCBs. Dr. Hennig believes that proper nutrition counseling should be considered by health officials and the medical community to reduce the overall risk for Superfund chemical toxicity and disease development. For More Information Contact: Bernhard HennigAnimal and Food Sciences 907 W. P. Garrigus Building (Office: 413) Lexington, KY 40546-0215 Tel: (859) 323-4933 Email: To learn more about this research, please refer to the following sources:
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75(1):47-56. 
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