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Immunochemical detection of sulfur mustard-adducts with DNA and proteins: Exploratory research on adducts with proteins

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Author: Schans, G.P. van der · Noort, D. · Mars-Groenendijk, R.H. · Dijk-Knijnenburg, H.C.M. van · Fidder, A. · Jong, L.P.A. de · Benschop, H.P.
Type:article
Date:2000
Source:BioScience 2000, US Army Medical Defense Bioscience Review, 4-9 June 2000, 976-985
Identifier: 526835
Keywords: Warfare · Adducts · DNA · Hemoglobin · Keratin · Dosimetry · Immunoassay · Sulfur mustard

Abstract

We have developed two modes of a standard operating procedure (SOP) for immunochemical detection of sulfur mustard adducts to DNA in human blood and skin. In the shortened mode data could be generated within 9 h after in vitro exposure of human blood to > 1 μM sulfur mustard. The sensitive mode allows detection of exposure to 50 nM sulfur mustard. The in vivo adduct level in blood in hairless guinea pigs remained constant during the first two weeks after administration of sulfur mustard (0.5 LD50, i.v.), whereas during the following two weeks it decreased to background level. The DNA adduct level in blood of a marmoset was initially in the same range but was decreased to marginal values at day 1 and 7. The DNA adduct level in skin after in vivo skin exposure of hairless guinea pigs had decreased 2- to 3-fold at 2 to 3 days after exposure; after 2 weeks the adduct level was only marginal but still detectable. The SOP could be set up and generate data within one day in an institute elsewhere (MRICD). Monoclonal antibodies have been obtained for adducts of sulfur mustard to hemoglobin and keratin (exposed to 50 μM sulfur mustard). Antibodies raised against adducts of sulfur mustard to keratin clearly showed binding to the horny layer of human skin exposed to a solution of 100 μM sulfur mustard or to saturated vapor of sulfur mustard for 1 min. This opens the way for development of a detection kit that can be applied directly to skin of personnel who are supposedly contaminated by sulfur mustard.