title: Investigation of cysteinyl protein adducts of benzene diolepoxide.
abstract: Metabolism of benzene is fairly complex yielding several reactive metabolites that could form adducts with macromolecules such as DNA and proteins. Systemic availability of these reactive species can be estimated by measuring the corresponding adducts of these species with serum albumin or hemoglobin. We have shown previously that serum albumin adducts of benzene oxide and 1,4-benzoquinone increased in a dose-dependent manner in rodents and humans exposed to benzene. However, formation of macromolecular adducts of other reactive metabolites, such as benzene diolepoxide and E,E-muconaldehyde, has not received much attention despite the demonstrated mutagenicity and/or carcinogenicity of these metabolites. We studied the reaction of isomers of benzene diolepoxide, namely syn-((+/-)BDE1) and anti-BDE ((+/-)BDE2), with sulfhydryl groups in vitro. The half-life of BDE2 in 0.1 M ammonium acetate buffer (pH 7.6) was (5.46 h) longer that that in serum albumin in the same buffer (3.83 h) indicating the reaction of BDE with nucleophilic sites on albumin. Reaction products between these and L-cysteine, and GSH were identified and characterized by mass spectrometry in an attempt to develop an assay to quantify these adducts in serum albumin.
authors.affiliation: Department of Environmental Sciences and Engineering, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7400, USA. suramya.unc.edu
authors.forename: Suramya
authors.initials: S
authors.lastname: Waidyanatha
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Rappaport
mesh_terms: D000089:Acetic Anhydrides; D001555:Benzene Derivatives / Q000737:chemistry / Q000378:metabolism*; D003545:Cysteine / Q000378:metabolism*; D004852:Epoxy Compounds / Q000737:chemistry / Q000378:metabolism*; D005463:Fluoroacetates; D008401:Gas Chromatography-Mass Spectrometry; D005978:Glutathione / Q000378:metabolism; D066298:In Vitro Techniques; D007536:Isomerism; D008698:Mesylates / Q000737:chemistry; D011485:Protein Binding; D012709:Serum Albumin / Q000378:metabolism; D014269:Trifluoroacetic Acid / Q000737:chemistry
chemical_list: D000089:Acetic Anhydrides; D001555:Benzene Derivatives; D004852:Epoxy Compounds; D005463:Fluoroacetates; D008698:Mesylates; D012709:Serum Albumin; C504215:benzene diolepoxide; C045880:methanesulfonic acid; C017958:trifluoroacetic anhydride; D014269:Trifluoroacetic Acid; D005978:Glutathione; D003545:Cysteine