DEPSCOR/97-98 Mechanisms and Biomonitoring of Toxicant-Induced Changes in Zinc Finger Proteins.

摘要

Human disease result from alterations in biochemical and genetic processes as well as from perturbations induced in these processes by toxic chemicals from the environment. The goals of this project were to understand alterations in gene expression mechanisms induced by toxic chemicals and to develop biomonitoring assays for such toxicants helpful for risk assessment. Inhibitory mechanisms of toxic chemicals on gene expression in vitro: The toxicants lead, mercury, and chromium were found to inhibit protein-DNA interactions involved in gene regulatory events by binding to the DNA binding domains of the proteins. Inhibitory mechanisms of toxic chemicals on gene expression in vivo: DNA array and proteomic studies were initiated on organs from rats exposed to lead ions or JP-8 jet fuel. Lead ions up-regulated oncogenes possible accounting for the carcinogenic potential of this compound. Significantly, JP-8 down-regulated a large number of rat intestinal genes and up-regulated genes in exposed lung tissues.