Metabolism of styrene oxide to styrene glycol in enriched mouse clara-cell preparations

J Toxicol Environ Health A. 2000 Dec 29;61(8):709-17. doi: 10.1080/00984100050195170.

Abstract

Styrene is a widely used chemical that has been shown to cause lung tumors in mice but not in rats. Styrene toxicity appears to be related to its bioactivation to styrene oxide, and this occurs almost exclusively in Clara cells. An important pathway in the detoxification of styrene oxide is via epoxide hydrolase to yield styrene glycol. When mouse Clara cells were incubated with racemic styrene oxide, R-styrene glycol was the predominant metabolite, giving an R/S ratio of 3.6. When the pure styrene oxide enantiomers were used as substrates, the corresponding styrene glycols were the predominant but not exclusive metabolites. Activity was slightly higher with the S-styrene oxide than with the R-styrene oxide. Addition of reduced glutathione to the incubation medium resulted in an increase in epoxide hydrolase activity, perhaps by decreasing oxidative stress. Mouse Clara cells thus show the capacity for detoxifying styrene oxide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biotransformation
  • Carcinogens / metabolism
  • Carcinogens / pharmacokinetics*
  • Cell Culture Techniques
  • Epoxy Compounds / metabolism
  • Epoxy Compounds / pharmacokinetics*
  • Ethylene Glycols / chemistry*
  • Glutathione / metabolism
  • Inactivation, Metabolic
  • Lung / cytology*
  • Lung / drug effects
  • Male
  • Mice
  • Oxidation-Reduction
  • Oxidative Stress

Substances

  • Carcinogens
  • Epoxy Compounds
  • Ethylene Glycols
  • styrene glycol
  • styrene oxide
  • Glutathione