PMID- 8792847 OWN - NLM STAT- MEDLINE DCOM- 19961022 LR - 20190819 IS - 0300-483X (Print) IS - 0300-483X (Linking) VI - 112 IP - 1 DP - 1996 Aug 1 TI - Teratogenic effects of the demethylating agent 5-aza-2'-deoxycytidine in the Swiss Webster mouse. PG - 37-43 AB - 5-Aza-2'-deoxycytidine (d-AZA) replaces cytidine in DNA thereby altering gene expression by passively removing methyl groups. This study determined the temporal patterns of morphological defects induced by d-AZA in mice. The dosages (0, 0.3, or 1.0 mg/kg) were administered by a single i.p. injection on gestational days (GD) 8, 9, 10, or 11. Mice were killed on GD 17 and fetal skeletons examined. The 1.0 mg/kg dose elicited characteristic defects for each treatment day: GD 8, supernumerary ribs, (significantly above background), fused vertebrae and ribs; GD 9, cleft palate and vertebral variations; GD 10, hind limb defects (especially phocomelia); GD 11, digital defects of fore and hindlimbs. The known demethylating ability of d-AZA coupled with the induction of longbone defects only in the hindlimbs suggests that d-AZA may act by disrupting specific hindlimb gene function through DNA hypomethylation. FAU - Branch, S AU - Branch S AD - North Carolina State University, Department of Toxicology, Raleigh 27695, USA. FAU - Francis, B M AU - Francis BM FAU - Brownie, C F AU - Brownie CF FAU - Chernoff, N AU - Chernoff N LA - eng PT - Journal Article PL - Ireland TA - Toxicology JT - Toxicology JID - 0361055 RN - 0 (Enzyme Inhibitors) RN - 0 (Teratogens) RN - 776B62CQ27 (Decitabine) RN - EC 2.1.1.- (DNA Modification Methylases) RN - M801H13NRU (Azacitidine) SB - IM MH - Analysis of Variance MH - Animals MH - Azacitidine/administration & dosage/*analogs & derivatives/toxicity MH - Cleft Palate/chemically induced/embryology MH - DNA Damage/genetics MH - DNA Modification Methylases/*antagonists & inhibitors MH - Decitabine MH - Dose-Response Relationship, Drug MH - Embryonic and Fetal Development/*drug effects MH - Enzyme Inhibitors/administration & dosage/*toxicity MH - Female MH - Gene Expression Regulation, Developmental/drug effects/genetics MH - Gestational Age MH - Hindlimb/drug effects/embryology MH - Injections, Intraperitoneal MH - Mice MH - Pregnancy MH - Ribs/drug effects/embryology MH - Spine/drug effects/embryology MH - Teratogens/*toxicity EDAT- 1996/08/01 00:00 MHDA- 1996/08/01 00:01 CRDT- 1996/08/01 00:00 PHST- 1996/08/01 00:00 [pubmed] PHST- 1996/08/01 00:01 [medline] PHST- 1996/08/01 00:00 [entrez] AID - 0300483X96881832 [pii] AID - 10.1016/0300-483x(96)88183-2 [doi] PST - ppublish SO - Toxicology. 1996 Aug 1;112(1):37-43. doi: 10.1016/0300-483x(96)88183-2.