Temporal changes in rat liver gene expression after acute cadmium and chromium exposure

PLoS One. 2015 May 19;10(5):e0127327. doi: 10.1371/journal.pone.0127327. eCollection 2015.

Abstract

U.S. Service Members and civilians are at risk of exposure to a variety of environmental health hazards throughout their normal duty activities and in industrial occupations. Metals are widely used in large quantities in a number of industrial processes and are a common environmental toxicant, which increases the possibility of being exposed at toxic levels. While metal toxicity has been widely studied, the exact mechanisms of toxicity remain unclear. In order to further elucidate these mechanisms and identify candidate biomarkers, rats were exposed via a single intraperitoneal injection to three concentrations of CdCl2 and Na(2)Cr(2)O(7), with livers harvested at 1, 3, or 7 days after exposure. Cd and Cr accumulated in the liver at 1 day post exposure. Cd levels remained elevated over the length of the experiment, while Cr levels declined. Metal exposures induced ROS, including hydroxyl radical (•OH), resulting in DNA strand breaks and lipid peroxidation. Interestingly, ROS and cellular damage appeared to increase with time post-exposure in both metals, despite declines in Cr levels. Differentially expressed genes were identified via microarray analysis. Both metals perturbed gene expression in pathways related to oxidative stress, metabolism, DNA damage, cell cycle, and inflammatory response. This work provides insight into the temporal effects and mechanistic pathways involved in acute metal intoxication, leading to the identification of candidate biomarkers.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cadmium / metabolism
  • Cadmium / toxicity*
  • Chromium / metabolism
  • Chromium / toxicity*
  • DNA Damage
  • Environmental Exposure
  • Gene Expression*
  • Lipid Metabolism
  • Liver / drug effects*
  • Liver / metabolism
  • Male
  • Oligonucleotide Array Sequence Analysis
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species / metabolism

Substances

  • Reactive Oxygen Species
  • Cadmium
  • Chromium

Associated data

  • GEO/GSE65198

Grant support

The research described herein was sponsored by the U.S. Army Medical Research and Materiel Command, Military Operational Medicine Research Program. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.