Paraoxonase (PON1) as a biomarker of susceptibility for organophosphate toxicity

Lucio G. Costa, Rebecca J. Richter, Wan Fen Li, Toby Cole, Marina Guizzetti, Clement E. Furlong

Research output: Contribution to journalArticle

102 Citations (Scopus)

Abstract

Paraoxonase (PON1) is an A-esterase capable of hydrolysing the active metabolites (oxons) of a number of organophosphorus (OP) insecticides such as parathion, diazinon and chlorpyrifos. PON1 activity is highest in liver and plasma, and among animal species significant differences exist, with birds and rabbits displaying very low and high activity respectively. Human PON1 has two polymorphisms in the coding region (Q192R and L55M) and five polymorphisms in the promoter region. The Q192R polymorphism imparts different catalytic activity toward some OP substrates, while the polymorphism at position -108 (C/T) is the major contributor to differences in the level of PON1 expression. Animal studies have shown that PON1 is an important determinant of OP toxicity, with animal species with a low PON1 activity having an increased sensitivity to OPs. Administration of exogenous PON1 to rats or mice protects them from the toxicity of OPs. PON1 knockout mice display a high sensitivity to the toxicity of diazoxon and chlorpyrifos oxon, but not paraoxon. In vitro assayed catalytic efficiencies of purified PON192 isoforms for hydrolysis of specific oxon substrates accurately predict the degree of in vivo protection afforded by each isoform. Low PON1 activity may also contribute to the higher sensitivity of newborns to OP toxicity.

Original languageEnglish (US)
Pages (from-to)1-12
Number of pages12
JournalBiomarkers
Volume8
Issue number1
DOIs
StatePublished - Jan 2003
Externally publishedYes

Fingerprint

Aryldialkylphosphatase
Organophosphates
Biomarkers
Polymorphism
Toxicity
Animals
Protein Isoforms
Diazinon
Paraoxon
Parathion
Chlorpyrifos
Esterases
Insecticides
Genetic Promoter Regions
Knockout Mice
Birds
Hydrolysis
Substrates
Metabolites
Liver

Keywords

  • Ecogenetics
  • Genetic polymorphisms
  • Organophosphate toxicity
  • Paraxonase (PON1)
  • Transgenic mice

ASJC Scopus subject areas

  • Biotechnology
  • Toxicology

Cite this

Paraoxonase (PON1) as a biomarker of susceptibility for organophosphate toxicity. / Costa, Lucio G.; Richter, Rebecca J.; Li, Wan Fen; Cole, Toby; Guizzetti, Marina; Furlong, Clement E.

In: Biomarkers, Vol. 8, No. 1, 01.2003, p. 1-12.

Research output: Contribution to journalArticle

Costa, Lucio G. ; Richter, Rebecca J. ; Li, Wan Fen ; Cole, Toby ; Guizzetti, Marina ; Furlong, Clement E. / Paraoxonase (PON1) as a biomarker of susceptibility for organophosphate toxicity. In: Biomarkers. 2003 ; Vol. 8, No. 1. pp. 1-12.
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