Germ cell mutagenicity of three metabolites of 1,3-butadiene in the rat: Induction of spermatid micronuclei by butadiene mono-, Di-, and diolepoxides in vivo
- Univ. of Turku (Finland)
- Inst. of Occupational Health, Helsinki (Finland)
Three metabolites of the industrial chemical 1,3-butadiene (BD), namely butadiene monoepoxide (BMO, 3,4-epoxy-1-butene), diepoxide (DEB, 1,2;3,4-diepoxybutane), and diolepoxide (DE, 3,4,-epoxybutane-1,2-dial) were studied for germ cell mutagenicity using the rat spermatid micronucleus (MN) test. All three epoxides increase slightly, but significantly, the frequency of spermatid MN. The most sensitive stage to the action of BMO and DEB was preleptotene (meiotic S phase) harvested at 18- daytime intervals after treatment. The dose-response for BMO followed a second order curve at this time interval, with maximum MN induction at the dose of 186 {mu}mol/kg and lower induction at higher doses. Late stages of the meiotic prophase (late pachytene-diplotene-diakinesis) also showed some sensitivity to the three epoxides. Stem cell spermatogonia were affected by DEB as observed by a slight induction of spermatid micronuclei 50 days after treatment. No clear cytotoxic effects were observed by measuring testicular weight or cell numbers of seminiferous epithelial state 1 18 days after the treatments. DEB at the dose 387 {mu}mol/kg caused a slight inhibition of spermatogonial DNA synthesis in stage 1 and a delay of meiotic DNA replication observed in stage XII 72 hr after treatment. Since BMO is able to induce spermatid MN in the rat, the present results, together with previous data, indicate that rat bone marrow MN results that are negative for both BD and BMO cannot directly predict mutagenicity in male germ cells. The results also emphasize that tissue, species-, and strain-specific differences in metabolism have to be taken into account when the genetic risks of human butadiene exposure are evaluated. The results support the conclusion that 1,3-butadiene is a germ cell mutagen-possibly also in humans. 42 refs., 2 figs., 6 tabs.
- Sponsoring Organization:
- USDOE
- OSTI ID:
- 530564
- Journal Information:
- Environmental and Molecular Mutagenesis, Journal Name: Environmental and Molecular Mutagenesis Journal Issue: 3 Vol. 29; ISSN 0893-6692; ISSN EMMUEG
- Country of Publication:
- United States
- Language:
- English
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