Diepoxybutane cytotoxicity on mouse germ cells is enhanced by in vivo glutathione depletion: A flow cytometric approach

  • Spanò M
  • Cordelli E
  • Leter G
 et al. 
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Abstract

Diepoxybutane is one of the key metabolites of butadiene, a compound of high environmental and occupational concern. The effects of diepoxybutane on mouse reproductive cells have been previously characterized by flow cytometry demonstrating a specific, dose-dependent cytotoxicity for differentiating spermatogonia. It is known that butadiene epoxides, deriving from butadiene bioactivation by cytochrome P450-monooxygenase systems, can be enzymatically conjugated to glutathione by glutathione S-transferases. In this paper, we tested the hypothesis whether a pretreatment with phorone, a well-known intracellular glutathione depleter, would enhance the germ cell cytotoxicity of diepoxybutane. Results were consistent with an active role played in vivo by the glutathione-detoxifying system, as diepoxybutane cytotoxicity was increased after chemically induced reduction of glutathione concentration.

Author-supplied keywords

  • Butadiene
  • Diepoxybutane
  • Flow cytometry
  • Glutathione
  • Phorone
  • Reproductive toxicology
  • Spermatogenesis

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