A Comparison of the Alkylating Capabilities of the Cysteinyl and Glutathionyl Conjugates of 1,2-Dichloroethane
Metabolic activation by glutathione conjugation of the dihaloethanes ethylene dichloride (EDC) and ethylene dibromide (EDB), continues to be important as these compounds are used commercially in enormous quantities and the mechanisms by which they exert toxicity and mutagenicity are not yet fully understood. The mutagenicity of EDC has been demonstrated to be dependent on the presence of cytosol and glutathione (Rannug et al., 1978). In line with this, is the observation of covalent association of EDC-derived radioactivity with polynucleotides in incubation mixtures containing cytosol, glutathione (GSH), and EDC (Guengerich et al., 1980). In the case of EDB, an alkylated purine has been isolated from similar incubation mixtures (Ozawa and Guengerich, 1983). These and other results with cofactors and inhibitors indicate that the GSH-transferases are initially responsible for the formation of important reactive intermediate(s) from these compounds.
KeywordsNuclear Magnetic Resonance Strand Scission Cysteine Conjugate Ethylene Dibromide Covalent Association
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