TY - JOUR
T1 - Teratogenic effects of the demethylating agent 5-aza-2'-deoxycytidine in the Swiss Webster mouse
AU - Branch, Stacy
AU - Francis, Bettina M.
AU - Brownie, Cecil F.
AU - Chernoff, Neil
PY - 1996/8/1
Y1 - 1996/8/1
N2 - 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.
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.
KW - 5-Aza-2'-deoxycytidine (DNA demethylating agent)
KW - Intraperitoneal injection
KW - Limb defects
KW - Swiss Webster (CD-1) mice
KW - Teratogenicity
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U2 - 10.1016/0300-483X(96)88183-2
DO - 10.1016/0300-483X(96)88183-2
M3 - Article
C2 - 8792847
AN - SCOPUS:0030221389
SN - 0300-483X
VL - 112
SP - 37
EP - 43
JO - Toxicology
JF - Toxicology
IS - 1
ER -