Protein tyrosine adduct in humans self-poisoned by chlorpyrifos

Bin Li, Peter Eyer, Michael Eddleston, Wei Jiang, Lawrence M Schopfer, Oksana Lockridge

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Studies of human cases of self-inflicted poisoning suggest that chlorpyrifos oxon reacts not only with acetylcholinesterase and butyrylcholinesterase but also with other blood proteins. A favored candidate is albumin because in vitro and animal studies have identified tyrosine 411 of albumin as a site covalently modified by organophosphorus poisons. Our goal was to test this proposal in humans by determining whether plasma from humans poisoned by chlorpyrifos has adducts on tyrosine. Plasma samples from 5 self-poisoned humans were drawn at various time intervals after ingestion of chlorpyrifos for a total of 34 samples. All 34 samples were analyzed for plasma levels of chlorpyrifos and chlorpyrifos oxon (CPO) as a function of time post-ingestion. Eleven samples were analyzed for the presence of diethoxyphosphorylated tyrosine by mass spectrometry. Six samples yielded diethoxyphosphorylated tyrosine in pronase digests. Blood collected as late as 5. days after chlorpyrifos ingestion was positive for CPO-tyrosine, consistent with the 20-day half-life of albumin. High plasma CPO levels did not predict detectable levels of CPO-tyrosine. CPO-tyrosine was identified in pralidoxime treated patients as well as in patients not treated with pralidoxime, indicating that pralidoxime does not reverse CPO binding to tyrosine in humans. Plasma butyrylcholinesterase was a more sensitive biomarker of exposure than adducts on tyrosine. In conclusion, chlorpyrifos oxon makes a stable covalent adduct on the tyrosine residue of blood proteins in humans who ingested chlorpyrifos.

Original languageEnglish (US)
Pages (from-to)215-225
Number of pages11
JournalToxicology and Applied Pharmacology
Volume269
Issue number3
DOIs
StatePublished - Jun 15 2013

Fingerprint

Chlorpyrifos
Tyrosine
Proteins
Plasmas
Butyrylcholinesterase
Albumins
Eating
Blood Proteins
Pronase
O,O-diethyl O-3,5,6-trichloro-2-pyridyl phosphate
Poisons
Biomarkers
Acetylcholinesterase
Poisoning
Mass spectrometry
Half-Life
Mass Spectrometry
Animals
Blood

Keywords

  • Albumin
  • Butyrylcholinesterase
  • Chlorpyrifos
  • Diethoxyphosphorylated tyrosine
  • Mass spectrometry
  • Poisoned patients

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Protein tyrosine adduct in humans self-poisoned by chlorpyrifos. / Li, Bin; Eyer, Peter; Eddleston, Michael; Jiang, Wei; Schopfer, Lawrence M; Lockridge, Oksana.

In: Toxicology and Applied Pharmacology, Vol. 269, No. 3, 15.06.2013, p. 215-225.

Research output: Contribution to journalArticle

Li, Bin ; Eyer, Peter ; Eddleston, Michael ; Jiang, Wei ; Schopfer, Lawrence M ; Lockridge, Oksana. / Protein tyrosine adduct in humans self-poisoned by chlorpyrifos. In: Toxicology and Applied Pharmacology. 2013 ; Vol. 269, No. 3. pp. 215-225.
@article{e72f2b8088e147538d418b63134c6c41,
title = "Protein tyrosine adduct in humans self-poisoned by chlorpyrifos",
abstract = "Studies of human cases of self-inflicted poisoning suggest that chlorpyrifos oxon reacts not only with acetylcholinesterase and butyrylcholinesterase but also with other blood proteins. A favored candidate is albumin because in vitro and animal studies have identified tyrosine 411 of albumin as a site covalently modified by organophosphorus poisons. Our goal was to test this proposal in humans by determining whether plasma from humans poisoned by chlorpyrifos has adducts on tyrosine. Plasma samples from 5 self-poisoned humans were drawn at various time intervals after ingestion of chlorpyrifos for a total of 34 samples. All 34 samples were analyzed for plasma levels of chlorpyrifos and chlorpyrifos oxon (CPO) as a function of time post-ingestion. Eleven samples were analyzed for the presence of diethoxyphosphorylated tyrosine by mass spectrometry. Six samples yielded diethoxyphosphorylated tyrosine in pronase digests. Blood collected as late as 5. days after chlorpyrifos ingestion was positive for CPO-tyrosine, consistent with the 20-day half-life of albumin. High plasma CPO levels did not predict detectable levels of CPO-tyrosine. CPO-tyrosine was identified in pralidoxime treated patients as well as in patients not treated with pralidoxime, indicating that pralidoxime does not reverse CPO binding to tyrosine in humans. Plasma butyrylcholinesterase was a more sensitive biomarker of exposure than adducts on tyrosine. In conclusion, chlorpyrifos oxon makes a stable covalent adduct on the tyrosine residue of blood proteins in humans who ingested chlorpyrifos.",
keywords = "Albumin, Butyrylcholinesterase, Chlorpyrifos, Diethoxyphosphorylated tyrosine, Mass spectrometry, Poisoned patients",
author = "Bin Li and Peter Eyer and Michael Eddleston and Wei Jiang and Schopfer, {Lawrence M} and Oksana Lockridge",
year = "2013",
month = "6",
day = "15",
doi = "10.1016/j.taap.2013.03.021",
language = "English (US)",
volume = "269",
pages = "215--225",
journal = "Toxicology and Applied Pharmacology",
issn = "0041-008X",
publisher = "Academic Press Inc.",
number = "3",

}

TY - JOUR

T1 - Protein tyrosine adduct in humans self-poisoned by chlorpyrifos

AU - Li, Bin

AU - Eyer, Peter

AU - Eddleston, Michael

AU - Jiang, Wei

AU - Schopfer, Lawrence M

AU - Lockridge, Oksana

PY - 2013/6/15

Y1 - 2013/6/15

N2 - Studies of human cases of self-inflicted poisoning suggest that chlorpyrifos oxon reacts not only with acetylcholinesterase and butyrylcholinesterase but also with other blood proteins. A favored candidate is albumin because in vitro and animal studies have identified tyrosine 411 of albumin as a site covalently modified by organophosphorus poisons. Our goal was to test this proposal in humans by determining whether plasma from humans poisoned by chlorpyrifos has adducts on tyrosine. Plasma samples from 5 self-poisoned humans were drawn at various time intervals after ingestion of chlorpyrifos for a total of 34 samples. All 34 samples were analyzed for plasma levels of chlorpyrifos and chlorpyrifos oxon (CPO) as a function of time post-ingestion. Eleven samples were analyzed for the presence of diethoxyphosphorylated tyrosine by mass spectrometry. Six samples yielded diethoxyphosphorylated tyrosine in pronase digests. Blood collected as late as 5. days after chlorpyrifos ingestion was positive for CPO-tyrosine, consistent with the 20-day half-life of albumin. High plasma CPO levels did not predict detectable levels of CPO-tyrosine. CPO-tyrosine was identified in pralidoxime treated patients as well as in patients not treated with pralidoxime, indicating that pralidoxime does not reverse CPO binding to tyrosine in humans. Plasma butyrylcholinesterase was a more sensitive biomarker of exposure than adducts on tyrosine. In conclusion, chlorpyrifos oxon makes a stable covalent adduct on the tyrosine residue of blood proteins in humans who ingested chlorpyrifos.

AB - Studies of human cases of self-inflicted poisoning suggest that chlorpyrifos oxon reacts not only with acetylcholinesterase and butyrylcholinesterase but also with other blood proteins. A favored candidate is albumin because in vitro and animal studies have identified tyrosine 411 of albumin as a site covalently modified by organophosphorus poisons. Our goal was to test this proposal in humans by determining whether plasma from humans poisoned by chlorpyrifos has adducts on tyrosine. Plasma samples from 5 self-poisoned humans were drawn at various time intervals after ingestion of chlorpyrifos for a total of 34 samples. All 34 samples were analyzed for plasma levels of chlorpyrifos and chlorpyrifos oxon (CPO) as a function of time post-ingestion. Eleven samples were analyzed for the presence of diethoxyphosphorylated tyrosine by mass spectrometry. Six samples yielded diethoxyphosphorylated tyrosine in pronase digests. Blood collected as late as 5. days after chlorpyrifos ingestion was positive for CPO-tyrosine, consistent with the 20-day half-life of albumin. High plasma CPO levels did not predict detectable levels of CPO-tyrosine. CPO-tyrosine was identified in pralidoxime treated patients as well as in patients not treated with pralidoxime, indicating that pralidoxime does not reverse CPO binding to tyrosine in humans. Plasma butyrylcholinesterase was a more sensitive biomarker of exposure than adducts on tyrosine. In conclusion, chlorpyrifos oxon makes a stable covalent adduct on the tyrosine residue of blood proteins in humans who ingested chlorpyrifos.

KW - Albumin

KW - Butyrylcholinesterase

KW - Chlorpyrifos

KW - Diethoxyphosphorylated tyrosine

KW - Mass spectrometry

KW - Poisoned patients

UR - http://www.scopus.com/inward/record.url?scp=84877002997&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84877002997&partnerID=8YFLogxK

U2 - 10.1016/j.taap.2013.03.021

DO - 10.1016/j.taap.2013.03.021

M3 - Article

C2 - 23566956

AN - SCOPUS:84877002997

VL - 269

SP - 215

EP - 225

JO - Toxicology and Applied Pharmacology

JF - Toxicology and Applied Pharmacology

SN - 0041-008X

IS - 3

ER -