Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Temporal Changes in Rat Liver Gene Expression after Acute Cadmium and Chromium Exposure

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 Na2Cr2O7, 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. Rats (5 per group) were exposed via a single intraperitoneal injection to three concentrations of CdCl2, Na2Cr2O7, or vehicle control,with livers harvested at 1, 3, or 7 days after exposure. Only the Cd mid dose and Cr high dose were selected for microarray analysis.

ORGANISM(S): Rattus norvegicus

SUBMITTER: Michael Madejczyk

PROVIDER: E-GEOD-65198 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

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

Madejczyk Michael S MS Baer Christine E CE Dennis William E WE Minarchick Valerie C VC Leonard Stephen S SS Jackson David A DA Stallings Jonathan D JD Lewis John A JA

PloS one 20150519 5

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 mechanis ...[more]

PMID: 25993096

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Project description:Our main objectives were: 1) to identify transcriptional signatures specific to the exposure to two metals: Ni and Cd; 2) to investigate the mechanisms of toxicity for these two metals; and 3) to develop a predictive tool to identify the sublethal effects of Ni and Cd contaminants in fish sampled from natural environments. The molecular mechanisms underlying nickel (Ni) and cadmium (Cd) toxicity and their specific effects on fish are poorly understood. Documenting gene transcription profiles offers a powerful approach towards identifying the molecular mechanisms affected by these metals and to discover biomarkers of their toxicity. However, confounding environmental factors can complicate the interpretation of the results and the detection of biomarkers for fish captured in their natural environment. In the present study, a 1000 candidate-gene microarray, developed from a previous RNA-seq study on a subset of individual fish from contrasting level of metal contamination, was used to investigate the transcriptional response to metal (Ni and Cd) and non metal (temperature, oxygen, and diet) stressors in yellow perch (Perca flavescens). Specifically, we aimed at 1) identifying transcriptional signatures specific to Ni and Cd exposure, 2) investigating the mechanisms of their toxicity, and 3) developing a predictive tool to identify the sublethal effects of Ni and Cd contaminants in fish sampled from natural environments. A total of 479 genes displayed significantly different transcription levels when temperature varied while 287 and 177 genes were differentially transcribed at different concentrations of Ni and Cd, respectively. These metals were found to mainly affect the transcription level of genes involved in iron metabolism, transcriptional and translational processes, vitamin metabolism, blood coagulation, and calcium transport. In addition, a linear discriminant analysis (LDA) made using gene transcription levels yielded 94% correctly reassigned samples regarding their level of metal contamination, which indicates the potential of the microarray to detect perch response to Cd or Ni effects.

Dataset Information

Temporal Changes in Rat Liver Gene Expression after Acute Cadmium and Chromium Exposure

Publications

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

Similar Datasets

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