Project Summary (1995-2000)

The overall purpose of this project is to investigate the effects of several heavy metals frequently found at Superfund waste sites on a family of heme-containing proteins called cytochrome P450, that are involved in the metabolism of toxic substances as well as many drugs and hormones. At high doses, lead and other metals decrease both the amount of total cytochrome P450 in the liver and the amounts of heme in red blood cells and liver. The mechanisms by which these decreases in cytochrome P450 and heme occur are being investigated, focusing on the study of individual metals alone and in combinations which are likely to be present at the waste sites, and on the identification of the role of metal-induced oxidative damage in these decreases. This research is also determining whether certain forms of cytochrome P450 are more susceptible to the effects of heavy metals than others. The purpose of these latter studies is to ascertain whether exposure to specific metals affects individuals' susceptibilities to drugs, hormones and other toxic substances metabolized by that particular form of P450.