title: 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 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.
authors.affiliation: ORISE Postdoctoral Fellow at the US Army Center for Environmental Health Research, Fort Detrick, MD, United States of America.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Madejczyk
authors.affiliation: Excet, Inc., Fort Detrick, MD, United States of America.
authors.forename: Christine E
authors.initials: CE
authors.lastname: Baer
authors.affiliation: US Army Center for Environmental Health Research, Fort Detrick, MD, United States of America.
authors.forename: William E
authors.initials: WE
authors.lastname: Dennis
authors.affiliation: National Institute for Occupational Safety and Health, Morgantown, WV, United States of America.
authors.forename: Valerie C
authors.initials: VC
authors.lastname: Minarchick
authors.affiliation: National Institute for Occupational Safety and Health, Morgantown, WV, United States of America.
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Leonard
authors.affiliation: US Army Center for Environmental Health Research, Fort Detrick, MD, United States of America.
authors.forename: David A
authors.initials: DA
authors.lastname: Jackson
authors.affiliation: US Army Center for Environmental Health Research, Fort Detrick, MD, United States of America.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Stallings
authors.affiliation: US Army Center for Environmental Health Research, Fort Detrick, MD, United States of America.
authors.forename: John A
authors.initials: JA
authors.lastname: Lewis
mesh_terms: D000818:Animals; D002104:Cadmium / Q000378:metabolism / Q000633:toxicity*; D002857:Chromium / Q000378:metabolism / Q000633:toxicity*; D004249:DNA Damage; D004781:Environmental Exposure; D015870:Gene Expression; D050356:Lipid Metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D002104:Cadmium; D002857:Chromium