Project Summary (2000-2005)

The goal of this project is to determine the mechanistic basis for the preferential effects of carcinogenic metals on inducible gene expression. Particularly, arsenic(III) and chromium(VI) are considered human lung carcinogens, and arsenic is also associated with an increased risk for skin, bladder and kidney cancer. Researchers are determining the mechanistic basis for the preferential effects of these carcinogenic metals on inducible gene expression. Previous studies demonstrated that arsenic and chromium have strong preferential effects on the expression of several model inducible genes at very low, non-toxic doses directly relevant to chronic human exposures. These gene-specific effects appear to be mediated, at least in part, by the ability of these metals to modulate specific transcription factors and cell signaling pathways that regulate the expression of these targeted genes. The specific objectives of this research are to determine the molecular basis for these effects, and the overall role of these gene alterations in the biological response to toxic metals.