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Sulfur mustard adducts

Noort, D., Fidder, A., Hulst, A.G., Wooffitt, A.R., Ash, D., and Barr, J.R. (2004). Retrospective detection of exposure to sulfur mustard improvements on an assay for liquid chromatography-tandem mass spectrometry analysis of albumin-sulfur mustard adducts. J. Anal. Toxicol., 28, 333-338. [Pg.26]

Figure 1. Sulfur mustard adduct formation with various nucleophiles... Figure 1. Sulfur mustard adduct formation with various nucleophiles...
Figure 4. Persistence of sulfur mustard adduct to N-terminal valine residue of hemoglobin in blood of a marmoset after sulfur mustard administration (4.1 mg/kg, i.v.) at t = 0. At the time points indicated blood samples were collected, globin was isolated and analyzed by using the modified Edman degradation for determination of the N-terminal valine adduct. Globin from human blood exposed to ris-sulfur mustard (10 iM) was used as an internal standard. (Reprinted from Toxicology and Applied Pharmacology, Vol. 184, D. Noort, H.P. Benschop and R.M. Black, Biomonitoring of Exposure to Chemical Warfare Agents A Review, pages 116-126 (2002), with permission from Elsevier Science.)... Figure 4. Persistence of sulfur mustard adduct to N-terminal valine residue of hemoglobin in blood of a marmoset after sulfur mustard administration (4.1 mg/kg, i.v.) at t = 0. At the time points indicated blood samples were collected, globin was isolated and analyzed by using the modified Edman degradation for determination of the N-terminal valine adduct. Globin from human blood exposed to ris-sulfur mustard (10 iM) was used as an internal standard. (Reprinted from Toxicology and Applied Pharmacology, Vol. 184, D. Noort, H.P. Benschop and R.M. Black, Biomonitoring of Exposure to Chemical Warfare Agents A Review, pages 116-126 (2002), with permission from Elsevier Science.)...
A sensitive method for analysis of the sulfur mustard adduct to this residue was developed on the basis of Pronase digestion of alkylated albumin to the tripeptide S-[2-[(hydroxyethyl)thio]ethyl-Cys-Pro-Phe, and detection using micro-LC/tandem MS (24) (see Figure 5). Albumin was isolated from... [Pg.438]

Figure 5. Procedure for analysis of sulfur mustard adduct to cysteine-34 residue in human serum albumin... Figure 5. Procedure for analysis of sulfur mustard adduct to cysteine-34 residue in human serum albumin...
G.P. Van der Schans, D. Noort, R.H. Mars-Groenendijk, A. Fidder, L.F. Chau, L.P.A. De Jong and H.P. Benschop, Immunochemical detection of sulfur mustard adducts with keratins in the stratum corneum of human skin, Chem. Res. Toxicol., 15, 21-25 (2003). [Pg.449]

Noort and colleagues (2008) investigated the persistence of sulfur mustard adducts to albumin and hemoglobin in rats. The albumin adduct (S -2-hydroxyethylthioethyl)-Cys-Pro-Tyr was detectable up to 7 days after the exposure, while the adduct to the N-terminal valine in hemoglobin was still detected after 28 days. The decrease of adduct concentration corresponded with albumin half-life and the hfetime of the rat erythrocyte, respectively. [Pg.778]

Assays for several other potential urinary analytes have been developed, but the analytes have yet to be confirmed in human exposed samples. N7-(2-hydroxyethylthioethyl) guanine is a breakdown product from alkylated DNA that has been observed in animal studies. Fidder et al. (1996a) developed both a GC-MS method that requires derivatization of the analyte and also a LC-MS-MS method that can analyze the compound directly. Other possible urinary analytes are an imidazole derivative formed from the reaction of sulfur mustard with protein histidine residues (Sandelowsky et al., 1992) and sulfur mustard adducts to metallothionien (Price et al., 2000). [Pg.518]

Analysis of Blood Samples. Urinary metabolites undergo relatively rapid elimination from the body, whereas blood components offer biomarkers that have the potential to be used for verification of sulfur mustard exposure long after the exposure incident. Three different approaches have been used for blood biomarker analysis. The intact macromolecule such as protein or DNA with the sulfur mustard adducts still attached can be analyzed. To date, this approach has only been demonstrated for hemoglobin using in vitro experiments. For proteins, an alternate approach is to enzymatically digest them to produce a smaller peptide with the sulfur mustard adduct still attached. Methods of this type have been developed for both hemoglobin and albumin. A third approach has been to cleave the sulfur mustard adduct from the macromolecule and analyze in a fashion similar to that used for free metabolites found in the urine. The later two approaches have both been successfully used to verify human exposure of sulfur mustard. [Pg.522]

Analytical Methods for Blood. Methods to measure sulfur mustard adducts to DNA in white blood cells have been developed using LC with fluorescence detection (Ludlum et al., 1994) and using an enzyme-linked immunosorbent assay (ELISA) (van der Schans et al., 1994, 2004). The DNA adduct that appears to be the most abundant results from sulfur mustard attachment to the N7 position of deoxyguaninosine (Fidder et al., 1994). The immunochemical method developed by van der Schans used monoclonal antibodies that were raised against N7-(2-hydroxyethylthioethyl)-guanosine-5 -phosphate. [Pg.522]

Van der Schans, Mars-Groenendijk, Bikker and Noort describe a standard operating procedure for an immunoslotblot assay of sulfur mustard adducts to DNA in human blood and skin for use in a field laboratory. [Pg.13]

The primary aim of the work presented in this chapter was the development of a procedure based on an immunoslotblot assay (ISB) for analysis of sulfur mustard adducts to DNA in human blood and skin, for use in a field laboratory. To this purpose, the various steps involved in the immunochemical assay have been simplified and minimized as much as possible for application under field conditions. A detailed standard operating procedure has been described elsewhere (4). [Pg.304]

Figure Chemical structure of the sulfur mustard adduct to the N7 position of 2 -deoxyguanosine. [Pg.305]

Procedure for immunoslotblot assay for analysis of sulfur mustard adducts to DNA in human blood... [Pg.306]

DNA denaturation and immunoslotblot procedure. The procedures were identical to the procedures described for sulfur mustard adducts to DNA in blood. [Pg.308]

In conclusion, a procedure for immunochemical analysis of the main sulfur mustard adduct to DNA in human white blood cells and skin has been developed, which can be easily performed in a field laboratory. [Pg.310]

Figure 4. Immunofluorescence microscopy of a cross-section of human skin exposed to saturated sulfur mustard vapor (1 min at 27 °C Ct 1040 mg.min.nr3 A) and of unexposed skin (B), using monoclonal antibody 1H10, directed against sulfur mustard adducts to human keratin, in a 1/50 dilution. The photographs are composed from an image obtained for FITC fluorescence (mainly emanating from the stratum corneum green) and from an image obtained for propidium iodide fluorescence representing DNA (red) in the same cross-section. (Reprinted with permission from G. R van der Schans et al., Chem. Res. Toxicol. 15, 21-25, 2002. Copyright (2002) American Chemical Society). Figure 4. Immunofluorescence microscopy of a cross-section of human skin exposed to saturated sulfur mustard vapor (1 min at 27 °C Ct 1040 mg.min.nr3 A) and of unexposed skin (B), using monoclonal antibody 1H10, directed against sulfur mustard adducts to human keratin, in a 1/50 dilution. The photographs are composed from an image obtained for FITC fluorescence (mainly emanating from the stratum corneum green) and from an image obtained for propidium iodide fluorescence representing DNA (red) in the same cross-section. (Reprinted with permission from G. R van der Schans et al., Chem. Res. Toxicol. 15, 21-25, 2002. Copyright (2002) American Chemical Society).
Sulfur mustard adducts were clearly detected in the stratum corneum whereas DNA counterstaining visualizes the presence of DNA in the nucleated cells. Hardly any fluorescence due to antibody treatment was measured over the nonexposed skin cross-section at the conditions used. In contrast to the immunochemical method for analysis of DNA-sulfiir mustard adducts, which involves laborious workup procedures, this approach opens the way for development of a rapid detection kit that can be applied directly to the skin. [Pg.313]

A standard operating procedure has been developed for an immunoslotblot assay of sulfur mustard adducts to DNA in human blood and skin for use in a field laboratory. A minimum detectable level of exposure of human blood in vitro > 50 nM sulfur mustard is feasible with the assay. In case of human skin, a 1 s exposure to saturated sulfur mustard vapor (830 mg.m3) could still be detected. [Pg.313]

Van der Schans, G.P., Mars-Groenendijk R.H, De Jong,L.P.A. Benschop, andNoort, D. (2004) Standard operating procedure for immunoslotblot assay for analysis of DNA/sulfur mustard adducts in human blood and skin. J. Analytical Toxicology 28, 316-319. [Pg.314]

LC-MS is a powerful method used to detect and quantify CWAs. The use of LC-MS for CWA and hydrolysis product detection has been reviewed [7,20,26]. LC-MS methods are often used to detect CWA hydrolysis/ degradation products instead of the active agents [27-28]. LC-MS serves as a bioanalytical method for CWA detection in living systems and its contributions have also been reviewed [7, 26, 29]. A LC-MS method using an on-line trypsin digestion is used to identify GB and sulfur mustard adducts with proteins and enzymes like human butyryl cholinesterase [30]. This technique, along with similar techniques, could be applied to confirm CWA exposure when illness is suspected from an unknown toxin. [Pg.443]

An excellent separation of five DNA nucleotides (2 -deoxyguanosine, 2 -deoxy-5-methylcytidine, 2 -deoxycytidine, 2 -deoxyadenosine) and their five sulfur mustard adducts (products fixim alleged mustard gas exposure) was generated on a C g column using a complex 40-min 0/100 ->48/52 methanol/water (25 mM ammonium carbonate buffer at pH 8) gradient [442]. Excellent peak shapes and resolution were obtained. [Pg.173]

Capacio et al. (2008) developed a method to detect sulfur mustard adducts in plasma proteins by hydro-lyzation (which produced TDG) and subsequent derivatization of TDG, followed by GS/MS analysis. The method was successfully applied to determine sulfur mustard adducts in rat plasma, following respiratory exposure to sulfur mustard. [Pg.845]


See other pages where Sulfur mustard adducts is mentioned: [Pg.24]    [Pg.46]    [Pg.435]    [Pg.436]    [Pg.438]    [Pg.439]    [Pg.441]    [Pg.832]    [Pg.832]    [Pg.522]    [Pg.525]    [Pg.525]    [Pg.526]    [Pg.529]    [Pg.548]    [Pg.548]    [Pg.155]   
See also in sourсe #XX -- [ Pg.304 , Pg.306 , Pg.307 , Pg.308 , Pg.313 ]




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