title: Immunodetection of serum albumin adducts as biomarkers for organophosphorus exposure.
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 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 S-[2-(diisopropylamino)ethyl]-O-ethyl methylphosphonothioate (VX), respectively, but did not recognize nonphosphonylated 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 GD) 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). mAb-HSA-GD could also detect serum albumin OP adducts in blood plasma samples from different animals administered GD, including rats, guinea pigs, and monkeys. 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 biologic approach to detect OP exposure in animals.
authors.affiliation: Human BioMolecular Research Institute, 5310 Eastgate Mall, San Diego, CA 92121, USA.
authors.forename: Sigeng
authors.initials: S
authors.lastname: Chen
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Lucille
authors.initials: L
authors.lastname: Lumley
authors.forename: John R
authors.initials: JR
authors.lastname: Cashman
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000941:Antigens / Q000737:chemistry / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D045744:Cell Line, Tumor; D002619:Chemical Warfare Agents / Q000737:chemistry / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004781:Environmental Exposure / Q000032:analysis*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D062025:Organophosphate Poisoning / Q000097:blood; D009943:Organophosphorus Compounds / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000737:chemistry / Q000378:metabolism*; D021241:Spectrometry, Mass, Electrospray Ionization; D014443:Tyrosine / Q000737:chemistry / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D000941:Antigens; D015415:Biomarkers; D002619:Chemical Warfare Agents; D009943:Organophosphorus Compounds; D012709:Serum Albumin; D014443:Tyrosine