Treatment of mouse zygotic or pregastrulation stages to 5-azacytidine produced embryonic death and fetal anomalies
- EPA, Washington, DC (United States)
- Oak Ridge National Laboratory, TN (United States)
- Children`s Hospital and Medical Center, Seattle, WA (United States)
Several studies have shown that the mouse zygote and the two-cell embryo are susceptible to the induction of congenital anomalies with certain genotoxic agents. The mechanisms by which the pathogenesis of these development defects arise are not known. In certain cases, it is possible that a nonconventional, perhaps epigenetic, mechanism is involved. To provide indirect evidence for this possibility, we conducted studies with 5-azacytidine (AzaC), an agent known to selectively activate transcription. Female mice were given a single ip injection of 20 mg/kg of AzaC at various postmating intervals to expose the zygotic and subsequent pregastrulation stages (i.e., 1 to 144 hrs post-mating). Females were killed on gestational day 17, the uterine contents scored and the live fetuses examined for external anomalies. AzaC treatment during 1 to 20 hrs after mating produced slight increases in embryonic death and in the incidence of fetal anomalies. The responses significantly increased with treatment at 25 hrs after mating. This interval corresponds approximately to the time when embryonic genes are beginning to be switched on. The frequency of fetal anomalies remained elevated at subsequent intervals until 64 hrs (blastocyst stage) when a further increase in the incidence of fetal anomalies occurred. Exposures after 64 hrs produced extreme embryoethality, thus, relatively lower doses were used. A stage dependent spectrum of anomalies were found which include anterior region affects of the fetus (e.g., exencephaly, eye defects, cleft palate, frontal nasal syndrome).
- OSTI ID:
- 88807
- Report Number(s):
- CONF-9405324-; ISSN 0893-6692; TRN: 95:004220-0011
- Journal Information:
- Environmental and Molecular Mutagenesis, Vol. 23, Issue Suppl.23; Conference: 25. annual meeting of the Environmental Mutagen Society, Portland, OR (United States), 7-12 May 1994; Other Information: PBD: 1994
- Country of Publication:
- United States
- Language:
- English
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