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Vesicants protein adducts

A number of adducts to amino acid residues have been identified by Noort and colleagues (1996) and Black et al. (1997a, b). Six different histidine residues, three glutamic acid residues, and both of the N-terminal valines were found. Alkylated cysteine, aspartic acid, lysine, and tryptophan were also detected. While the N1 and N3 histidine adducts were found to be most abundant, it was the alkylated N-terminal valine adducts that were most useful for subsequent quantification. See Detection of DNA and protein adducts of vesicants, below, for analytical details. [Pg.778]

Once incorporated, unbound lewisite is quickly hydrolyzed. Its predominant metabolite is 2-chlorovinylarsonous acid, CVAA (Figure 50.8). Analytical methods to confinn lewisite exposure have, at least in the past, focused on the detection and quantification of CVAA. However, Noort et al. (2002) also pointed out that due to the high affinity of arsenic towards sulfhydryl groups, adducts of lewisite/ CVAA and cysteine residues of proteins are formed. In an in vitro study, incubating " C-labeled lewisite with human blood samples, 90% of lewisite was found in erythrocytes, whereas 25 to 50% of arsenic was bound to globin. From these protein adducts, CVAA can be released to form an adduct with the antidote British Anti-Lewisite (BAL) (Fidder et al, 2000). The authors were also able to identify a specific protein adduct of lewisite formed with the cysteine residues 93 and 112 of P-globin. See Detection of DNA and protein adducts of vesicants, below, for analytical... [Pg.781]

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. [Pg.128]

From these protein adducts, CVAA can be released to form an adduct with the antidote British anti-lewisite (BAL Fidder et al., 2000). The authors were also able to identify a specific protein adduct of lewisite formed with cysteine residues 93 and 112 of p-globin. See the section "Detection of DNA and protein adducts of vesicants," later in tiiis chapter, for analytical details. Figure 56.8 summarizes the biotransformation and reversal of adduct formation by BAL. [Pg.848]

Vesicants, nerve agents, and phosgene are reactive electrophiles that react covalently with nucleophilic sites on macro molecules. Reactive nucleophilic sites exist on the bases and phosphate groups of DNA molecules. An advantage of DNA as a substrate is that it is present in all tissues of the body. A disadvantage is that repair mechanisms tend to excise the alkylated moiety, resulting in a much shorter lifetime compared to alkylated proteins (for a recent review of mass spectrometry for quantitation of DNA adducts, see Koc and Swen-berg <2>). [Pg.434]

Sulfur mustard (mustard gas) remains one of the CW agents of greatest concern because of its ease of production, favorable physicochemical properties, and potent vesicant action. It is a bifunctional alkylating agent, which reacts rapidly under physiological conditions with nucleophilic sites in proteins and DNA to form covalent adducts, via an intermediate episulfonium ion (see Figure 1). In the sections below, the various adducts (as unambiguously elucidated in recent years by mass spectrometry) are addressed, and methods for their analysis are discussed. [Pg.435]

The use of sulfur mustard as a vesicant CW agent implies that proteins of the skin are a primary target. It was found that upon exposure of human callus to [14C]sulfur mustard, a significant part of the radioactivity was covalently bound to keratin (30). Most of the radioactivity (80%) bound to keratin could be removed by treatment with alkali, indicating the presence of adducts to glutamic and/or aspartic acid residues. [Pg.484]


See other pages where Vesicants protein adducts is mentioned: [Pg.526]    [Pg.129]    [Pg.849]    [Pg.40]    [Pg.296]    [Pg.903]    [Pg.536]    [Pg.818]   
See also in sourсe #XX -- [ Pg.782 ]




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