Biological markers protein adducts

Adducts with macromolecules such as proteins offer long lived biological markers of exposure, possibly up to several months. 

Adducts with macromolecules, particularly proteins, offer long-lived biological markers of exposure to Chemical Warfare Agent (CWA), possibly up to several months. Gas or liquid chromatography combined with tandem mass spectrometry, are the methods of choice for unequivocal identification of these adducts or metabolites at trace levels. Several... 

As described below, urinary metabolites have been identified for vesicants, nerve agents, 3-quinuclidinyl benzilate (BZ), hydrogen cyanide and the RCAs, CS, CR and capsaicin. Protein adducts have been identified for vesicants, nerve agents and phosgene, and DNA adducts for sulphur and nitrogen mustards. With the rapid advances being made in proteomics and metabo-nomics, new biological markers of exposure will undoubtedly be identified in the near future. 

Pryor and coworkers have shown that peroxynitrite-mediated nitrosations and nitrations of phenols are modulated by CO2. The reaction was found to be first order with respect to peroxynitrite and zero order with respect to phenol, showing that an activated intermediate of peroxynitrite, perhaps the peroxynitrite anion-C02 adduct (0=N—OO—C02 ), is involved as the intermediate (equation 57) . At pH higher than 8.0, 4-nitrosophenol is the major product, whereas in acidic media significant amounts of the 2- and 4-nitrophenols were formed. Peroxynitrite also induces biological nitration of tyrosine residues of the proteins. The detection of 3-nitrotyrosine is routinely used as an in vivo marker for the production of the cytotoxic species peroxynitrite (ONOO ). It was shown that nitrite anion (N02 ) formed in situ by the reaction of nitric oxide and hypochlorous acid (HOCl) is similarly able to nitrate phenolic substrates such as tyrosine and 4-hydroxyphenylacetic acid . 

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