Exposure to PCBs destroys cell connections in the gut.
Choi, YJ, MJ Seelbach, H Pu, SY Eum, L Chen, B Zhang, B Hennig, M Toborek. 2010. Polychlorinated biphenyls disrupt intestinal integrity via NADPH oxidase-induced alterations of tight junction protein expression. Environmental Health Perspectives http://dx.doi.org/10.1289./ehp.0901751.
A family of common environmental contaminants, PCBs, can damage and break the important protein links between cells that line the intestine and form a protective barrier into the body. The breaks allow the chemicals to move through the outer buffer cells and "leak" into surrounding tissues where they may cause the systemic toxic health effects associated with the compounds.
This is the first study to identify a specific way that PCBs damage these vital cell connections – called tight junctions – and get into the body where they circulate in blood and accumulate in tissues.
Even though food is a main source of PCB exposure, little is known about their direct effects on the gut, where nutrient absorption and enzyme digestion occur in the small intestine epithelial cells. The tight junction proteins that connect the neighboring cells form barriers against contaminants as well as provide communication paths between individual cells within tissues.
The loss of the protein connections between the cells is associated with many diseases, including diabetes, allergies, asthma and autoimmune diseases. This study suggests that PCBs may contribute to the gut problems that are linked to these health problems.
PCBs are a global environmental pollutant that do not easily break down. Even though many areas of the world are phasing them out of use, they still contaminate water and land where they were used mainly as coolants and lubricants, including the Great Lakes region, a fishing hot spot.
Human exposure occurs mainly through food, especially through contaminated fish. Exposure to PCBs can affect brain development and IQ and is associated with a number of broader, whole-body effects.
The study examined PCBs' effects on gut cells using both cell cultures and mice – to determine if the cell effects were consistent in whole organisms. Researchers exposed colon cancer cells to four different PCBs at concentrations of 1-10 micromoles. These concentrations do not kill cells and are similar to levels measured in human blood after a short-term exposure. Fluorescence was used to track the cellular proteins affected by these chemicals and to determine if they were related to the tight junctions.
The adult male mice were given PCBs directly into the stomach through a feeding tube to simulate exposure from food. They were exposed to amounts that produced similar PCB-blood concentrations as the cell cultures exposures. Intestinal tissue was examined a day after the exposures. Permeability of the gut tissues was assessed by tracking a fluorescent sugar test molecule also administered directly into the stomach.
All of the PCBs increased the amount of test molecules that passed through the cultured cells. The main proteins that were affected – NADPH oxidase and zonula occludens-1 (ZO-1) – pointed to disruption of the tight junction.
When the mice were exposed, the gut wall lost its ability to contain test particles. A closer look confirmed that the junctions between the cells were damaged as measured by the loss of ZO-1.
