The incidence of 5-azacytidine-induced
exencephaly was compared between MT/HokIdr strain (MT) and Slc:ICR strain (ICR) mice. MT mice have a
genetic predisposition for
exencephaly, but ICR mice do not. Pregnant mice were given
5-azacytidine (1 mg/kg to 100 micrograms/kg) injected intraperitoneally on Day 7.5 of gestation (vaginal plug day = Day 0.5), and fetuses were observed for external malformations on Day 18.5 of gestation. One hundred micrograms/kg
5-azacytidine induced
exencephaly in MT mice but not in ICR mice, and 1 mg/kg
5-azacytidine resulted in resorptions in MT mice but caused
exencephaly in ICR mice. These results indicated that MT mice had 10-fold more sensitivity to
5-azacytidine than ICR mice. It seems likely that less than effective doses of
teratogens for animals without
genetic predispositions are still effective in inducing malformations in animals with a
genetic predisposition for malformations. When 4-somite-stage embryos of both MT and ICR mice were cultured in rat serum supplemented with
5-azacytidine, 0.02 micrograms/ml
5-azacytidine induced the failure of closure of cephalic neural tube in MT embryos but not in ICR embryos, and 0.2 micrograms/ml
5-azacytidine induced severe growth retardation in MT embryos but in ICR embryos it only induced embryos with smaller heads and fewer somites than in control. These results indicated that MT mouse embryos in culture also had a 10-fold-increased sensitivity to
5-azacytidine compared with ICR mouse embryos, suggesting maternal effects play no significant role in their increased sensitivity to
5-azacytidine.