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Immunodetection of Serum Albumin Adducts as Biomarkers for Organophosphorus Exposure.


J Pharmacol Exp Ther. 2012 Nov 28;


Authors: Chen S, Zhang J, Lumley L, Cashman JR


Abstract

A major challenge in organophosphate (OP) research has been the identification and utilization of reliable biomarkers for the rapid, sensitive and efficient detection of OP exposure. Although tyrosine (Tyr) 411 OP adducts to human serum albumin (HSA) have been suggested to be one of the most robust biomarkers in the detection of OP exposure, the analysis of HSA-OP adduct detection has been limited to techniques using mass spectrometry. Herein, we describe the procurement of two monoclonal antibodies (mAb-HSA-GD and mAb-HSA-VX) that recognized the HSA Tyr 411 adduct of soman (GD) or VX, respectively, but did not recognize non-phosphonylated HSA. We showed that mAb-HSA-GD was able to detect the HSA Tyr 411 OP adduct at a low level (i.e., human blood plasma treated with 180 nM soman) that could not be detected by mass spectrometry. mAb-HSA-GD and mAb-HSA-VX showed an extremely low level detection of GD-adducted to HSA (on the order of picograms or 10-12 g). mAb-HSA-GD could also detect serum albumin OP adducts in blood plasma samples from different animals administered GD including rat, guinea pig and monkey. The ability of the two antibodies to selectively recognize nerve agents adducted to serum albumin suggests that these antibodies could be used to identify biomarkers of OP exposure and provide a new biological approach to detect OP exposure in animals.

PMID: 23192655 [PubMed - as supplied by publisher]