Accession Number:

ADA439134

Title:

Biochemical Markers for Exposure to Low Doses of Organophosphorus Insecticides

Descriptive Note:

Final rept. 1 Aug 2001-31 Jul 2005

Corporate Author:

NEBRASKA UNIV AT OMAHA

Personal Author(s):

Report Date:

2005-08-01

Pagination or Media Count:

119.0

Abstract:

The acute toxicity of organophosphorus agents OP is explained by inhibition of acetyicholinesterase AChE. However, toxicity from low dose exposure is not understood. Using mass spectroscopy, we developed the hypothesis that multiple targets for each OP exist, and that target identity varies with the OP. Thus, dichlorvos covalently binds to acetylcholinesterase, butyryloholinesterase, platelet-activating factor acetylhydrolase alpha 2, and acylpeptide hydrolase. FP-biotin binds not only to these proteins, but also to albumin, platelet-activating factor acetylhydrolase alpha 1, esterase 10, and fatty acid amide hydrolase. Covalent binding to a set of proteins is hypothesized to explain low dose toxicity. Each OP is hypothesized to bind to a slightly different set, and therefore to have a unique mechanism of toxicity. In vivo studies in mice with a biotinylated OP showed 12 OP labeled proteins in mouse blood. The most intensely labeled protein was albumin, thus identifying albumin as a new biomarker of OP exposure. People partially deficient in AChE are expected to be healthy and fertile, but to be unusually sensitive to OP. Our studies with AChE deficient mice predict that some cases of low dose toxicity will be explained by partial AChE deficiency in humans.

Subject Categories:

  • Biochemistry
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE