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.
Spanò, M., Cordelli, E., Leter, G., & Pacchierotti, F. (1998). Diepoxybutane cytotoxicity on mouse germ cells is enhanced by in vivo glutathione depletion: A flow cytometric approach. Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, 397(1), 37–43. https://doi.org/10.1016/S0027-5107(97)00193-0