The Activating Role of Glutathione in the Mutagenicity of 1,2-Dibromoethane

  • P. J. van Bladeren
  • D. D. Breimer
  • G. M. T. Rotteveel-Smijs
  • J. J. Hoogeterp
  • G. R. Mohn
  • A. de Groot
  • A. A. van Zeeland
  • A. van der Gen
Part of the Advances in Experimental Medicine and Biology book series (AEMB)

Abstract

1,2-Dibromoethane (DBE) is widely used as an insecticide, fungicide and gasoline additive.1 A number of adverse effects of this compound have been reported, notably its mutagenicity towards bacteria2 and carcinogenicity towards rats and mice.3 Apart from its direct alkylating ability, two mechanisms for these toxic actions can be envisaged, both of which involve biotransformation. The first one consists of oxidation, followed by loss of hydrogen bromide, leading to bromoacetaldehyde, a highly reactive substance which can bind covalently to macromolecules.4, 5 However, bromoacetaldehyde has been reported to be non-mutagenic.6 The second possible mechanism involves conjugation to glutathione (GSH). As has been shown for 1,2-dichloroethane7 and cis-1,2-dichlorocyclohexane,8 the 2-halogenothioether resulting from substitution of one of the halogen atoms by glutathione is responsible for enhanced mutagenic activity of these compounds in the presence of GSH and GSH-S-transferases (see Fig. 1).

Keywords

Covalent Binding Sulfur Mustard Direct Conjugation Mercapturic Acid Hydrogen Bromide 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 1982

Authors and Affiliations

  • P. J. van Bladeren
    • 1
  • D. D. Breimer
    • 1
  • G. M. T. Rotteveel-Smijs
    • 1
  • J. J. Hoogeterp
    • 1
  • G. R. Mohn
    • 1
  • A. de Groot
    • 1
  • A. A. van Zeeland
    • 1
  • A. van der Gen
    • 1
  1. 1.Departments of Pharmacology, Radiation Genetics and Chemical Mutagenesis, and Organic ChemistryUniversity of LeidenLeidenThe Netherlands

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