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

Madejczyk, Michael S.; Baer, Christine E.; Dennis, William E.; Minarchick, Valerie C.; Leonard, Stephen S.; Jackson, David A.; Stallings, Jonathan D.; Lewis, John A.; Zhu, Donghui

doi:10.1371/journal.pone.0127327

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

Journal Article · Tue May 19 00:00:00 EDT 2015 · PLoS ONE

DOI:https://doi.org/10.1371/journal.pone.0127327· OSTI ID:1627751

Madejczyk, Michael S. ^[1]; Baer, Christine E. ^[2]; Dennis, William E. ^[3]; Minarchick, Valerie C. ^[4]; Leonard, Stephen S. ^[4]; Jackson, David A. ^[3]; Stallings, Jonathan D. ^[3]; Lewis, John A. ^[3]; Zhu, Donghui ^[5]

US Army Center for Environmental Health Research, Fort Detrick, MD ( United States)
Excet, Inc., Fort Detrick, MD (United States)
US Army Center for Environmental Health Research, Fort Detrick, MD (United States)
National Institute for Occupational Safety and Health (NIOSH), Morgantown, WV (United States)
North Carolina A & T State Univ., Greensboro, NC (United States)

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.

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Research Organization:: Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN (United States)

Sponsoring Organization:: USDOE; U.S. Army

Grant/Contract Number:: SC0014664

OSTI ID:: 1627751

Journal Information:: PLoS ONE, Vol. 10, Issue 5; ISSN 1932-6203

Publisher:: Public Library of ScienceCopyright Statement

Country of Publication:: United States

Language:: English

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Effects of metals cadmium and chromium alone and in combination on the liver and kidney tissue of male Spraque-Dawley rats: An ultrastructural and electron-energy-loss spectroscopy investigation: V enter et al . Venter, Chantelle; Oberholzer, Hester Magdalena; Cummings, Franscious Riccardo Microscopy Research and Technique, Vol. 80, Issue 8 https://doi.org/10.1002/jemt.22877	journal	April 2017

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