Project Summary (2000-2006)

The health effects of Superfund chemicals are critically dependent on the amount of biologically active chemical taken up into animals from environmental sources. While physico-chemical properties are known to influence xenobiotic absorption, the extent of biotransformation in the intestine, the presence of other xenobiotics, the composition of the ingested materials and the interactions of the chemical with intestinal transport proteins also influence the amount taken up from ingested material. The long-term objective of this project is to understand factors governing the uptake and biotransformation of environmental xenobiotics. The Superfund chemicals benzo(a)pyrene (BaP), 3,3’,4,4’-tetrachlorobiphenyl (TCB), methoxychlor (MCH) and the model compound nonylphenol ethoxylate (NPE) are being investigated with studies conducted in vitro, in situ and in vivo in channel catfish and rats. In addition, the effects of exposure to these chemicals on the absorption of two drug substrates, cyclosporin and tetracycline, are being investigated. Project investigators are also studying the roles that the plasma membrane efflux transporter (P-glycoprotein (pgp)) and biotransformation enzymes in the intestine have on the systemic bioavailability of toxicants encountered in the diet.