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ToxSci Advance Access published online on November 3, 2004
Toxicological Sciences, doi:10.1093/toxsci/kfi023
Toxicological Sciences © Society of Toxicology 2004; all rights reserved
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Received September 5, 2004
Accepted October 23, 2004

Neurotoxicology

Albumin, a New Biomarker of Organophosphorus Toxicant Exposure, Identified by Mass Spectrometry

Eric S. Peeples 1, Lawrence M. Schopfer 1, Ellen G. Duysen 1, Reggie Spaulding 2, Troy Voelker 2, Charles M. Thompson 2, and Oksana Lockridge 1*

1 University of Nebraska Medical Center, Eppley Institute, Omaha, NE 68198-6805
2 University of Montana, Department of Biomedical and Pharmaceutical Sciences, Missoula, MT 59812

* To whom correspondence should be addressed.
Oksana Lockridge, E-mail: olockrid{at}unmc.edu


  Abstract

The classical laboratory tests for exposure to organophosphorus toxicants (OP) are inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity in blood. In a search for new biomarkers of OP exposure, we treated mice with a biotinylated organophosphorus agent, FP-biotin. The biotinylated proteins in muscle were purified by binding to avidin-Sepharose, separated by gel electrophoresis, digested with trypsin, and identified from their fragmentation patterns on a quadrupole time of flight mass spectrometer. Albumin and ES1 carboxylesterase (EC 3.1.1.1) were found to be major targets of FP-biotin. These FP-biotinylated proteins were also identified in mouse plasma by comparing band patterns on nondenaturing gels stained for albumin and carboxylesterase activity, with band patterns on blots hybridized with Streptavidin Alexa-680. Two additional FP-biotin targets, AChE (EC 3.1.1.7) and BChE (EC 3.1.1.8), were identified in mouse plasma by finding that enzyme activity was inhibited 50-80%. Mouse plasma contained eight additional FP-biotinylated bands whose identity has not yet been determined. In vitro experiments with human plasma showed that chlorpyrifos oxon, echothiophate, malaoxon, paraoxon, methyl paraoxon, diazoxon, diisopropylfluorophosphate, and dichlorvos competed with FP-biotin for binding to human albumin. Though experiments with purified albumin have previously shown that albumin covalently binds OP, this is the first report of OP binding to albumin in a living animal. Carboxylesterase is not a biomarker in man because humans have no carboxylesterase in blood. It is concluded that OP bound to albumin could serve as a new biomarker of OP exposure in man.

Keywords: acetylcholinesterase; butyrylcholinesterase; organophosphate; FP-biotin; albumin.
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