5-AZA-2'-Deoxycytidine-Induced Dysmorphogenesis in the Rat

Stacy Branch, N. Chernoff, C. Brownie, B. Magnus Francis

Research output: Contribution to journalArticle

Abstract

5-aza-2'-deoxycytidine (d-AZA) causes temporally related defects in the developing mouse. Treatment of 1.0 mg/kg on gestation day (GD) 8 results in axial skeletal defects; on GD9, cleft palate and vertebral defects; on GD10, hindlimb phocomelia; and on GD11, digital defects. An unusual aspect of d-AZA teratogenicity in mice is that the phocomelia appears to be specific to the hindlimb, and the forelimb is not similarly affected regardless of treatment day. The current study was initiated to evaluate the embryonic response of another species, the rat, to this unique teratogen. Pregnant Sprague Dawley (CD) rats were treated with d-AZA or vehicle control. The compound was administered i.p. on GD9, 10, 11, or 12 to parallel developmental staging of the mouse. The highest dose (1.0 mg/kg) elicited effects indicating increased sensitivity to the compound in the rat as compared to the mouse. GD9 treatment was characterized by massive resorptions; GD10, by a predominance of axial skeletal defects and cleft palate; GD11, by a predominance of forelimb phocomelia and missing ribs; and GD12 by hindlimb phocomelia and forelimb digit defects. These data indicate significant differences in the developmental responses to d-AZA of the mouse and the rat. This may reflect interspecies differences in the temporal expression of genes involved in morphogenesis and/or the methylation patterns of such genes. Molecular data generated in the mouse will be compared to that of the rat to further characterize the developmental dynamics responsible for the interspecies differences.

Original languageEnglish (US)
Pages (from-to)329-338
Number of pages10
JournalTeratogenesis Carcinogenesis and Mutagenesis
Volume19
Issue number5
DOIs
StatePublished - Oct 16 1999

Keywords

  • Axial skeletal malformations
  • Cytidine analog
  • Interspecies differences
  • Limb malformations
  • Teratogenicity

ASJC Scopus subject areas

  • Oncology
  • Genetics
  • Toxicology
  • Genetics(clinical)
  • Health, Toxicology and Mutagenesis

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