Superfund Research Program
Bioavailability of Chlorinated Hydrocarbons in the Diet
Chlorinated hydrocarbons are a diverse group of persistent environmental contaminants that include polychlorinated biphenyls (PCBs), 2,3,7,8-TCDD and a number of pesticides. Widely dispersed in rivers, lakes and other freshwater systems throughout the country, these chemicals tend to bioaccumulate in the food chain, increasing in concentration as they are passed along to successive levels. For animals that depend on contaminated bodies of water for food, the diet can be a significant source of exposure to chlorinated hydrocarbon compounds.
Whether any toxicity is produced in the body from ingesting these compounds is dependent in part on the amount of chemical that is absorbed into the bloodstream during passage through the digestive tract. Once in the digestive tract, chlorinated hydrocarbons may be taken up into intestinal cells by several processes including diffusion, which is the passive movement of a chemical from a place of high concentration to one of low concentration. From intestinal cells, the chemicals may be transferred to blood or excreted back into the intestine. While the contribution of diffusion has been recognized as important for absorption of chlorinated hydrocarbons, less is known about the significance of other mechanisms of uptake and excretion.
Researchers at the University of Florida have been investigating factors that may affect the bioavailability of chlorinated hydrocarbons in the diet. The intestinal uptake of the persistent PCB, 3,3',4,4'-tetrachlorobiphenyl (TCB), was studied with the channel catfish (Ictalurus punctatus) as the animal model. Some studies were conducted in situ with isolated sections of intestinal loop, which served as a model of contaminant uptake across intestinal membranes into the systemic circulation. Other studies were conducted in vitro with subcellular metabolizing fractions collected from the intestinal tract.
The in situ studies demonstrated that the uptake of TCB from the intestinal lumen (cavity) was variable. Two factors were shown to be important in determining uptake: the composition of the diet in which the TCB was introduced into the intestinal cavity, and whether the animals were pre-exposed to TCB. If the TCB was readily dissolved in the dietary matrix, more was transported across the intestine into the bloodstream, suggesting that dietary composition could influence uptake of TCB. If animals were pre-exposed to TCB, less of a subsequent dose was taken up, suggesting a saturable process was involved in TCB uptake, in addition to simple diffusion.
In vitro studies showed that TCB causes several changes in protein expression in the intestine that could affect bioavailability. A protein that is involved in the efflux transport of chemicals out of intestinal cells into the lumen, p-glycoprotein, was induced in the lower intestine by TCB. This finding suggests that exposure to this chemical may reduce uptake of xenobiotics and perhaps endogenous substances that are substrates for this efflux transporter protein. TCB also increased levels of some forms of glutathione S-transferase, an enzyme thought to be involved in intracellular transport of xenobiotics and the movement of lipophilic xenobiotics through intestinal cells.
Another goal of this research has been to understand whether the intestine is involved in the biotransformation of chlorinated hydrocarbons to metabolites that are absorbed into the bloodstream more or less readily than the parent compound. While the intestine typically has a lower capacity for xenobiotic metabolism than the liver, the intestine's metabolic activity has been recognized in recent years as a possible influence on contaminant bioavailability.
Studies by this group of researchers showed that there was very little biotransformation of TCB in the intestine in either untreated or pre-treated fish, so the variability in uptake observed for TCB was due solely to changes in uptake of the parent compound.
Ingestion is an important route of exposure to environmental contaminants and the digestive tract is an important site of contaminant absorption in the body. There has also been a growing awareness that the small intestine has highly specialized functions, including metabolism and transport of xenobiotic compounds, which may influence the bioavailability of environmental contaminants present in the diet. However, our understanding of these processes is still very limited.
These studies are significant, then, for providing new insight into the dietary factors and cellular level processes that may affect the intestinal bioavailability of chlorinated hydrocarbons in the diet. Determining the ease with which these chemicals move from the digestive tract into intestinal cells and the circulatory system is important for determining the risk they pose to consumers of contaminated foods.
For More Information Contact:
To learn more about this research, please refer to the following sources:
- Doi AM, Kleinow KM, James MO, Venugopalan CS, Holmes E. 1998. Bioavailability and biotransformation of 3,4,3',4'-tetrachlorobiphenyl (TCB) in in situ intestinal preparations of uninduced and TCB-induced channel catfish. Toxicol Sci 42:337.
- Kleinow KM, James MO, Tong Z, Venugopalan CS. 1998. Bioavailability and biotransformation of benzo(a)pyrene in an isolated perfused in situ catfish intestinal preparation. Environ Health Perspect 106:155-166. PMID:9449680
To receive monthly mailings of the Research Briefs, send your email address to email@example.com.