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1677561 
Journal Article 
Metal interactions in mice under environmental stress 
García-Sevillano, MA; Jara-Biedma, R; González-Fernández, M; García-Barrera, T; Gómez-Ariza, JL 
In Press 
Yes 
BioMetals
ISSN: 0966-0844
EISSN: 1572-8773 
26 
651-666 
English 
A metallomic analytical approach based on the use of size exclusion chromatography coupled to ICP-MS has been used to obtain metal profiles related to overexpression or inhibition of metal-binding biomolecules, which is connected to exposure experiment of laboratory mice Mus musculus to toxic metals, such as Cd, Hg and As. Exposure to Cd induces the formation of Cd-metallothionein in liver that reveals the protective role of this organ; however, exposure to Hg reduces the intensity of the peak associated to Cu-superoxide dismutase (Cu-SOD) while Hg-SOD peak increases, which suggests the competence of Cu and Hg for the active sites of SOD in liver that causes mercury translocation to kidney, in which the concentration of Hg as Hg-metallothionein increases drastically to be excreted by urine. It has been also observed the protective effect of selenium on mercury toxicity in blood plasma, which produces decreasing of the intensity of Se-protein in plasma with Hg exposure and correlative increases of Hg-albumin that transport mercury to kidney for excretion. Finally, arsenic exposure provokes the accumulation of small metabolites of this element, such as dimethylarsenic and monomethylarsenic for excretion. The application of the metallomic approach to liver extracts from free-living mouse Mus spretus shows the overexpression of Cu, Zn and Cd-peaks at 7 kDa (related to metal-metallothionein) in environmental contaminated sites, as well as the increase of peaks related to Cu- and Zn-SOD and Zn-albumin. However, in kidney, can be checked the presence of high concentration of arsenic small metabolites in contaminated areas, similarly to results found in exposure experiments. In addition, the application of a metabolomic approach based on direct infusion mass spectrometry to organ extracts (liver, kidney and serum) from mice (M. musculus) exposed to arsenic reveals important metabolic changes related to antioxidative activity, membrane cell damage, energy metabolism and arsenic elimination. Similar results were obtained from free-living mouse (M. spretus) from areas contaminated with arsenic. The integration of metallomics and metabolomics results provides a more comprehensive evaluation about the biological response in exposure experiments to toxic metals as well as in environmental assessment of contamination. 
Biological response; Metallomics; Metabolomics; Mus musculus; Mus spretus; ICP-MS; Direct infusion mass spectrometry 
IRIS
• Arsenic Hazard ID
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     2. Lit Search Updates through Oct 2015
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     7. Other Studies through Oct 2015
          MOA
• Arsenic (Inorganic)
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     4. Adverse Outcome Pathways/Networks Screening
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• Arsenic MOA
     4. Adverse Outcome Pathways
          Oxidative stress related effects (includes non-specific SH reactions)
     1. MOA Literature Screening
          Health Effect Screening
• Arsenic Susceptibility
     1. Susceptibility Literature Screening
          Keyword Search
     2. Excluded
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