Teratogenicity of 5‐azacytidine in the Sprague‐Dawley rat

Abstract

5‐Azacytidine (5‐aza), a chemical that is incorporated into DNA and RNA with consequent alterations in the expression of mammalian genes, was administered to pregnant Sprague‐Dawley rats on single days during gestation. Doses of 0.5, 1, and 2 mg/kg were given by intraperitoneal injection on d 9, 10, 11, or 12. Dams were killed on d 20 of gestation and fetuses were examined for both external and skeletal defects. 5‐Azacytidine affected development on all days tested. The compound was embryolethal, caused reductions in fetal weight, and had profound effects on morphological development. Digit and limb anomalies, exencephaly, micrognathia, gastroschisis, and various rib defects were observed and related to the day of exposure.