The small intestine is a major portal of entry for drugs and carcinogens. The mucosal cells of this organ contain microsomal mixed function oxidases and cytosolic glutathione S-transferases, both of which are inducible with xenobiotic exposure. This proposal is designed to assess the following: (1) the role of the glutathione S-transferases and glutathione in drug metabolism and drug absorption. Using reversed intestinal loops and intact rats the role of binding to the transferases and glutathione conjugation will be studied; (2) the hypothesis of a mucosal-block theory for carcinogens, such as polycyclic aromatic hydrocarbons, will be tested. According to this hypothesis carcinogen oxidation in the intestine leads to fixation to mucosal cell constituents and elimination by desquamation during the normal turnover of cells. The influence in vitro and in vivo of a variety of environmental agents on these two research areas will be studied, including starvation, feeding, charcoal-broiled food, presence or absence of bile acids, exposure to agents known to induce intestinal microsomal and cytosol drug metabolism. These studies are aimed at a better understanding of the functions of the small intestine as a drug absorbing and drug metabolizing organ and a potential barrier to carcinogens.