Immunodetection of Serum Albumin Adducts as Biomarkers for Organophosphorus Exposure s
نویسندگان
چکیده
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-HSAGD and mAb-HSA-VX showed an extremely low-level detection of GD adducted to HSA (on the order of picograms). mAb-HSAGD 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.
منابع مشابه
JPET #201368 1 Immunodetection of Serum Albumin Adducts as Biomarkers for Organophosphorus Exposure*
متن کامل
Immunodetection of serum albumin adducts as biomarkers for organophosphorus exposure.
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 tec...
متن کاملMycotoxin Adducts on Human Serum Albumin: Biomarkers of Exposure to Stachybotrys chartarum
OBJECTIVE Despite the growing body of evidence showing adverse health effects from inhalation exposure to the trichothecene-producing mold Stachybotrys chartarum, controversy remains. Currently, there are no reliable assays suitable for clinical diagnosis of exposure. We hypothesized that satratoxin G (SG) -albumin adducts may serve as biomarkers of exposure to this fungus. DESIGN We studied ...
متن کاملShort Communication Quantitative Comparison of Aflatoxin B1 Serum Albumin Adducts in Humans by Isotope Dilution Mass Spectrometry and ELISA
Metabolic activation of the hepatocarcinogenic mycotoxin aflatoxin B1 (AFB1) results in the covalent attachment of AFB1 to serum albumin. Digestion of adducted albumin releases AFB1-lysine, a biomarker of exposure status. AFalbumin adducts have been most frequently measured in precipitated serum albumin using an immunoassay (ELISA); however, a sensitive and specific isotope dilution mass spectr...
متن کاملProtein adducts as biomarkers of exposure to organophosphorus compounds.
Exposure to organophosphorus (OP) compounds can lead to serious neurological damage or death. Following bioactivation by the liver cytochromes P450, the OP metabolites produced are potent inhibitors of serine active-site enzymes including esterases, proteases and lipases. OPs may form adducts on other cellular proteins. Blood cholinesterases (ChEs) have long served as biomarkers of OP exposure ...
متن کامل