|Title||Diepoxybutane cytotoxicity on mouse germ cells is enhanced by in vivo glutathione depletion: A flow cytometric approach|
|Publication Type||Articolo su Rivista peer-reviewed|
|Year of Publication||1998|
|Authors||Spanò, M., Cordelli Eugenia, Leter Giorgio, and Pacchierotti Francesca|
|Journal||Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis|
|Keywords||animal cell, Animalia, Animals, article, butadiene diepoxide, Butadienes, Cell cycle, cell differentiation, Cytotoxicity, DNA, drug effect, Environmental Pollution, enzyme activation, Epoxy Compounds, Flow cytometry, Fluorescent Dyes, Germ Cells, glutathione, glutathione metabolism, Inbred Strains, Indoles, Ketones, male, Mice, mouse, Mutagens, nonhuman, Organ Size, Ploidies, priority journal, Spermatids, spermatogenesis|
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.
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