Induction and transmission of chromosome aberrations in mouse oocytes after treatment with butadiene diepoxide

A study was conducted on the genotoxicity of butadiene diepoxide (DEB) in mouse oocytes. Superovulated female mice were injected intraperitoneally with DEB and mated with untreated males. Oocyte exposure occurred approximately 1.5 days before ovulation. DEB doses ranged between 26 and 52 mg/kg. Chromosome aberrations were scored in C-banded metaphases of one-cell embryos. The percentage of mated females, the average number of zygotes harvested per female, the frequencies of unfertilized oocytes and developmentally delayed zygotes did not reveal any overt sign of chemical toxicity which hindered the propensity of animals to mate or affected the ovulation, fertilization, or cell cycle progression of treated oocytes. A dose-dependent induction of chromosome aberrations was observed which was best fitted by a linear quadratic equation. Half of all the aberrations transmitted by DEB-treated oocytes were chromatid-type breaks or exchanges. Among chromosome-type aberrations, double fragments far exceeded chromosome exchanges. This spectrum of structural aberrations differed markedly from what was previously observed in one-cell embryos conceived by DEB-treated sperm, where 97% were chromosome-type aberrations and 40% were dicentrics or translocations. This difference suggests that chromosome damage in one-cell embryos can be fixed by different mutagenic pathways influenced by the targeted gamete and its specific chromatin configuration. After exposure to the same dose, oocytes transmitted to one-cell embryos between 4 and 8 times fewer aberrations than DEB-treated sperm. While the rate of aberration induction suggests that female germ cells may be less at risk than mature sperm,especially at low-dose levels, the higher threshold for reproductive toxicity observed in female than in male mice may justify inclusion of data on female germ cell mutagenicity in the genetic risk assessment of butadiene exposure. Environ. Mol. Mutagen. 30:403–409, 1997 © 1997 Wiley-Liss, Inc.