Chapter

Paraoxonases in Inflammation, Infection, and Toxicology

Volume 660 of the series Advances in Experimental Medicine and Biology pp 61-71

Date:

Identification and Characterization of Biomarkers of Organophosphorus Exposures in Humans

  • Jerry H. KimAffiliated withDepartment of Anesthesiology, University of Washington
  • , Richard C. StevensAffiliated withDepartment of Medicine (Division of Medical Genetics) and Genome Sciences, University of WashingtonAberdeen Proving Ground
  • , Michael J. MacCossAffiliated withDepartments of Genome Sciences, University of Washington
  • , David R. GoodlettAffiliated withDepartments of Medicinal Chemistry, University of Washington
  • , Alex ScherlAffiliated withDepartments of Medicinal Chemistry, University of Washington
  • , Rebecca J. RichterAffiliated withAberdeen Proving GroundDepartment of Medicine (Division of Medical Genetics) and Genome Sciences, University of Washington
  • , Stephanie M. SuzukiAffiliated withDepartment of Medicine (Division of Medical Genetics) and Genome Sciences, University of Washington
  • , Clement E. FurlongAffiliated withDepartment of Medicine (Division of Medical Genetics) and Genome Sciences, University of Washington Email author 

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Abstract

Over 1 billion pounds of organophosphorus (OP) chemicals are manufactured worldwide each year, including 70 million pounds of pesticides sprayed in the US. Current methods to monitor environmental and occupational exposures to OPs such as chlorpyrifos (CPS) have limitations, including low specificity and sensitivity, and short time windows for detection. Biomarkers for the OP tricresyl phosphate (TCP), which can contaminate bleed air from jet engines and cause an occupational exposure of commercial airline pilots, crewmembers and passengers, have not been identified.

The aim of our work has been to identify, purify, and characterize new biomarkers of OP exposure. Butyrylcholinesterase (BChE) inhibition has been a standard for monitoring OP exposure. By identifying and characterizing molecular biomarkers with longer half-lives, we should be able to clinically detect TCP and OP insecticide exposure after longer durations of time than are currently possible.

Acylpeptide hydrolase (APH) is a red blood cell (RBC) cytosolic serine proteinase that removes N-acetylated amino acids from peptides and cleaves oxidized proteins. Due to its properties, it is an excellent candidate for a biomarker of exposure. We have been able to purify APH and detect inhibition by both CPS and metabolites of TCP. The 120-day lifetime of the RBC offers a much longer window for detecting exposure. The OP-modified serine conjugate in the active site tryptic peptide has been characterized by mass spectrometry.

This research uses functional proteomics and enzyme activities to identify and characterize useful biomarkers of neurotoxic environmental and occupational OP exposures.

Keywords

Butyrylcholinesterase Acylpeptide hydrolase Biomarkers of OP exposure Mass spectrometry Affinity purification Immunomagnetic beads