Exposure to Nickel, Chromium, or Cadmium Causes Distinct Changes in the Gene Expression Patterns of a Rat Liver Derived Cell Line

Many heavy metals, including nickel, cadmium, and chromium are toxic industrial chemicals with an exposure. While these substances are known to produce adverse health effects leading to health problems, the detailed mechanisms remain unclear. To elucidate the processes involved in the toxicity of these metals at the molecular level and to perform a comparative analysis, H4-II-E-C3 rat liver-derived cell lines were treated with each metal and gene expression patterns were determined. We identified both common and unique biological responses to exposure to the metals. All three metals induced oxidative stress. Although all three metals are known to be genotoxic, evidence for DNA damage in our study only exists in response to chromium. Nickel induced a hypoxic response as well as inducing genes involved in chromatin structure. Cadmium distinctly perturbed genes related to endoplasmic reticulum stress and invoked the unfolded protein response leading to apoptosis. With these studies, we have completed the first gene expression comparative analysis of nickel, cadmium, and chromium in H4-II-E-C3 cells. Prepared in collaboration with Excert Inc., Fort Detrick, MD.