Phosphylated tyrosine in albumin as a biomarker of exposure to organophosphorus nerve agents.
The organophosphorus nerve agents sarin, soman, cyclosarin and tabun phosphylate a tyrosine residue on albumin in human blood. These adducts may offer relatively long-lived biological markers of nerve agent exposure that do not 'age' rapidly, and which are not degraded by therapy with oximes. Sensitive methods for the detection of these adducts have been developed using liquid chromatography-tandem mass spectrometry. Adducts of all four nerve agents were detected in the blood of exposed guinea pigs being used in studies to improve medical countermeasures. The tyrosine adducts with soman and tabun were detected in guinea pigs receiving therapy 7 days following subcutaneous administration of five times the LD(50) dose of the respective nerve agent. VX also forms a tyrosine adduct in human blood in vitro but only at high concentrations.
Williams
Nichola H
NH
Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire, SP4 0JQ, UK.
Harrison
John M
JM
Read
Robert W
RW
Black
Robin M
RM
D000418:Albumins / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002619:Chemical Warfare Agents / Q000633:toxicity*; D002801:Cholinesterase Reactivators / Q000494:pharmacology; D006168:Guinea Pigs; D006801:Humans; D009943:Organophosphorus Compounds / Q000633:toxicity*; D010091:Oximes / Q000494:pharmacology; D011485:Protein Binding; D014443:Tyrosine / Q000378:metabolism*
D000418:Albumins; D015415:Biomarkers; D002619:Chemical Warfare Agents; D002801:Cholinesterase Reactivators; D009943:Organophosphorus Compounds; D010091:Oximes; D014443:Tyrosine