Effect of Soluble Nickel Exposure on Iron-Mediated Gene Transcription and Enzyme ActivityEPA Grant Number: FP916418
Title: Effect of Soluble Nickel Exposure on Iron-Mediated Gene Transcription and Enzyme Activity
Investigators: Davidson, Todd L.
Institution: New York University
EPA Project Officer: Manty, Dale
Project Period: January 1, 2004 through December 31, 2006
Project Amount: $111,172
RFA: STAR Graduate Fellowships (2004) RFA Text | Recipients Lists
Research Category: Fellowship - Toxicology , Academic Fellowships , Health Effects
Nickel is a dangerous environmental and occupational pollutant. The mechanism of nickel-induced lung injury and carcinogenesis is not completely clear. The objective of this research project is to determine the effects of soluble nickel on iron-dependent cellular processes including both iron-regulated gene transcription and enzyme activity.
Nickel is known to stabilize the hypoxia inducible factor-1 (HIF-1) protein, which is thought to be important in tumor progression. Because nickel affects HIF-1, which is controlled by an iron-dependent enzyme, we designed in vitro experiments using the Affymetrix Gene Chip to look at the effect of nickel on iron-dependent processes in mouse embryo fibroblasts. Several gene families whose expression is mediated by iron were changed by exposure to soluble nickel. We will further characterize these changes in human lung cells using the Affymetrix Gene Chip to analyze transcriptional changes, and Western blots to look at changes in protein levels. In addition, cellular iron levels, the activity of iron containing enzymes, and the uptake of iron in cells exposed to nickel also will be investigated. Data obtained from this research may give new insight into the mechanisms of nickel-induced carcinogenesis, as well as contribute important information for the treatment and prevention of occupational diseases.