Impact of nutrition on PCB toxicity.

Studies are evolving which suggest that nutritional intervention can modify pathologies of diseases associated with environmental toxic insults. The diet is a major route of exposure to environmental toxins, such as persistent organic pollutants and heavy metals. Many persistent organics, such as polychlorinated biphenyls (PCBs), bioaccumulate in our bodies and "bioremediation" is extremely difficult. Furthermore, many environmental toxins induce signaling pathways that are oxidative stress-sensitive and similar or the same as the ones associated with the etiology and early pathology of many chronic diseases. There is now increasing evidence that exposure to PCBs can contribute to the development of inflammatory diseases such as atherosclerosis. Activation, chronic inflammation, and dysfunction of the vascular endothelium are critical events in the initiation and acceleration of atherosclerotic lesion formation. Our studies indicate that an increase in cellular oxidative stress and an imbalance in antioxidant status are critical events in PCB-mediated induction of inflammatory genes and endothelial cell dysfunction. We also have evidence that the plasma membrane microdomains called caveolae play an important role in endothelial activation and toxicity mediated by coplanar PCBs. Caveolae are particularly abundant in endothelial cells and play a major role in endothelial trafficking and the regulation of signaling pathways associated with the pathology of vascular diseases. There is a great need to further explore this nutritional paradigm in environmental toxicology and to improve our understanding of the relationship between nutrition and lifestyle, exposure to environmental toxins and disease. Our studies suggest that certain dietary fats can increase the risk of environmental insult induced by PCBs, while other dietary factors may provide protection. Nutrition may provide the most sensible means to develop primary intervention and prevention strategies of diseases associated with many environmental toxic insults.