EXPOSURE TO NICKEL, CHROMIUM, OR CADMIUM CAUSES DISTINCT CHANGES IN THE GENE EXPRESSION PATTERNS OF RAT LIVER-DERIVED CELL LINES

Abstract

Nickel, cadmium, and chromium are toxic industrial chemicals with an exposure risk, found in military, occupational, and environmental settings. While the substances are known to have adverse health effects, the exact mechanisms of toxicity remain unclear and a paucity of biomarkers of exposure and effect exist. To identify candidate biomarkers and to elucidate the mechanisms of toxicity of Ni, Cr, and Cd, H4-II-E-C3 and MH1C1 rat liver-derived cell lines were treated with various concentrations of each metal and gene expression patterns were determined through the use of an Affymetrix microarray and analyzed using bioinformatic tools including Ingenuity Pathway Analysis. A total of 992 probe sets were differentially expressed as a result of exposure to nickel, chromium, and/or cadmium, 246 of which may be further investigated as candidate biomarkers. The modulated genes were involved in biological processes such as the oxidative stress response, apoptosis, cell cycle regulation, and hypoxia.