Micronuclei are induced in rat spermatids in vitro by 1,2,3,4-diepoxybutane but not by 1,2-epoxy-3-butene and 1,2-dihydroxy-3,4-epoxybutane

The genotoxic effects of three 1,3-butadiene metabolites, 1,2-epoxy-3-butene (monoepoxide, EB), 1,2,3,4-diepoxy-butane (diepoxide, DEB) and 1,2-dihydroxy-3,4-epoxy-butane (diolepoxide, DiolEB), on male rat germ cells were studied by the meiotic micronucleus method in vitro. Seminiferous tubular segments from stages XII to XIII containing late pachytene-diakinetic spermatocytes were cultivated in the presence of the test chemical for 4 days. During the culture, spermatocytes passed through meiotic divisions and developed into early spermatids in which micronuclei could be scored. DEB was found to be a very potent micronucleus inducer in rat meiosis. All concentrations tested (5–20 μM) were able to cause a statistically significantly higher frequency of micronuclei (P < 0.05) compared with controls and a linear dose-dependent trend for micronucleus induction was seen (P < 0.01). However, EB and DiolEB caused no increase in micronucleus frequencies in spermatids at the concentrations tested (100–1000 μM for EB and 10–100 μM for DiolEB) and at higher concentrations cytotoxic effects were seen upon dividing cells causing a significant reduction in the number of spermatids. According to these results DEB is the most genotoxic butadiene metabolite in rat germ cells during meiosis.