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-diepoxybutane (diepoxide, DEB) and 1,2-dihydroxy-3,4-epoxybutane (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 microM) 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 microM for EB and 10-100 microM 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.
Sjöblom
T
T
Department of Medical Genetics, University of Turku, Finland.
Lähdetie
J
J
D000818:Animals; D002070:Butadienes / Q000378:metabolism / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004852:Epoxy Compounds / Q000378:metabolism / Q000633:toxicity*; D006018:Glycols / Q000378:metabolism / Q000633:toxicity*; D008297:Male; D008540:Meiosis / Q000187:drug effects; D015162:Micronucleus Tests / Q000379:methods*; D009153:Mutagens / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013087:Spermatids / Q000187:drug effects*
D002070:Butadienes; D004852:Epoxy Compounds; D006018:Glycols; D009153:Mutagens; C080053:3,4-epoxybutane-1,2-diol; C024370:3,4-epoxy-1-butene; C007366:diepoxybutane; C031763:1,3-butadiene