INDUCTION AND TRANSMISSION OF CHROMOSOME-ABERRATIONS IN MOUSE OOCYTESAFTER TREATMENT WITH BUTADIENE DIEPOXIDE

A study was conducted on the genotoxicity of butadiene diepoxide (DEB) in mouse oocytes. Superovulated female mice were injected intraperito neally with DEB and mated with untreated males. Oocyte exposure occurr ed approximately 1.5 days before ovulation. DEB doses ranged between 2 6 and 52 mg/kg. Chromosome aberrations were scored in C-banded metapha ses of one-cell embryos. The percentage of mated females, the average number of zygotes harvested per Female, the frequencies of unfertilize d 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 progress ion of treated oocytes. A dose-dependent induction of chromosome aberr ations was observed which was best Fitted by a linear-quadratic equati on. Half of all the aberrations transmitted by DEB-treated oocytes wer e chromatid-type breaks or exchanges. Among chromosome-type aberration s, double fragments far exceeded chromosome exchanges. This spectrum o f structural aberrations differed markedly from what was previously ob served in one-cell embryos conceived by DEB-treated sperm, where 97% w ere chromosome-type aberrations and 40% were dicentrics or translocati ons. This difference suggests that chromosome damage in one-cell embry os can be fixed by different mutagenic pathways influenced by the targ eted gamete and its specific chromatin configuration. After exposure t o the same dose, oocytes transmitted to one-cell embryos between 4 and 8 times fewer aberrations than DEB-treated sperm. While the rate of a berration induction suggests that female germ cells may be less at ris k than mature sperm, especially at low-dose levels, the higher thresho ld for reproductive toxicity observed in female than in male mice may justify inclusion of data on female germ cell mutagenicity in the gene tic risk assessment of butadiene exposure. (C) 1997 Wiley-Liss, Inc.