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Author Notes:

Correspondence: Dean P. Jones, Ph.D., Director, Clinical Biomarkers Laboratory, Division of Pulmonary, Allergy and Critical Care Medicine, 615 Michael Street, Suite 205P, Emory University, Atlanta, GA 30322; Phone: 1-404-727-5970; Fax: 404-712-2974; Email: dpjones@emory.edu

Disclosures: The authors declare that they have no competing financial interests.

Subject:

Research Funding:

This research was supported in part by NIH Grants ES016731, ES011195, AG038746, RR025008, HD46501; RR00165, HL083019, HL070892, RR023356

Keywords:

  • metabolomics
  • plasma
  • mass spectrometry
  • probability-based modularity clustering
  • exposome

High-performance metabolic profiling of plasma from seven mammalian species for simultaneous environmental chemical surveillance and bioeffect monitoring

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Journal Title:

Toxicology

Volume:

Volume 295, Number 1-3

Publisher:

, Pages 47-55

Type of Work:

Article | Post-print: After Peer Review

Abstract:

High-performance metabolic profiling (HPMP) by Fourier-transform mass spectrometry coupled to liquid chromatography gives relative quantification of thousands of chemicals in biologic samples but has had little development for use in toxicology research. In principle, the approach could be useful to detect complex metabolic response patterns to toxicologic exposures and to detect unusual abundances or patterns of potentially toxic chemicals. As an initial study to develop these possible uses, we applied HPMP and bioinformatics analysis to plasma of humans, rhesus macaques, marmosets, pigs, sheep, rats and mice to determine: 1) whether more chemicals are detected in humans living in a less controlled environment than captive species, and 2) whether a subset of plasma chemicals with similar inter-species and intra-species variation could be identified for use in comparative toxicology. Results show that the number of chemicals detected was similar in humans (3221) and other species (range 2537 to 3373). Metabolite patterns were most similar within species and separated samples according to family and order. A total of 1485 chemicals were common to all species; 37% of these matched chemicals in human metabolomic databases and included chemicals in 137 out of 146 human metabolic pathways. Probability-based modularity clustering separated 644 chemicals, including many endogenous metabolites, with inter-species variation similar to intra-species variation. The remaining chemicals had greater inter-species variation and included environmental chemicals as well as GSH and methionine. Together, the data suggest that HPMP provides a platform that can be useful within human populations and controlled animal studies to simultaneously evaluate environmental exposures and biological responses to such exposures.

Copyright information:

© 2012 Elsevier Ireland Ltd. All rights reserved.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported License (http://creativecommons.org/licenses/by-nc-nd/3.0/).

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