Metabolism of Vinyl Halides: In Vitro Studies on Roles of Potential Activated Metabolites

  • F. Peter Guengerich
Part of the Advances in Experimental Medicine and Biology book series (AEMB)

Abstract

Vinyl chloride (VC) has been shown to be toxic and carcinogenic in animals and humans (Maltoni and Lefemine, 1974). Vinyl bromide (VBr) also appears to be hepatotoxic and carcinogenic (Conolly et al., 1978). Barbin et al. (1975) indicated that both VC and VBr can be activated to reactive electrophiles by liver microsomal systems fortified with NADPH. A number of other studies strongly suggest that mixed-function oxidation of vinyl halides is responsible for the mutagenesis and irreversible binding of metabolites that is observed with these compounds (Bartsch and Montesano, 1975; Bolt et al., 1975; Hefner et al., 1975; Henschler and Bonse, 1977; Guengerich and Watanabe, 1979). A commonly suggested reactive metabolite is a 2-haloethylene oxide. However, such compounds rearrange to 2-haloacetaldehydes, which also react with potential nucleophilic targets. In the studies presented here, we examined the ability of highly purified enzymes to specifically destroy these postulated reactive intermediates in situ in microsomal incubation systems, utilizing irreversible binding of vinyl halide labels to protein and DNA as indices of activation.

Keywords

Hydrolysis Glutathione Adenosine Pyridine Adduct 

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Copyright information

© Springer Science+Business Media New York 1982

Authors and Affiliations

  • F. Peter Guengerich
    • 1
  1. 1.Department of Biochemistry and Center in Environmental ToxicologyVanderbilt UniversityNashvilleUSA

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