Dose‐related Induction of Digital Malformations in Rats by 5‐Azacytidine: Description of the Defects

Abstract Dose‐related changes of 5‐azacytidine (5‐AC) induced digital malformations are reported. Dosages of 0.4, 0.5, 0.6, 0.7, and 1.0 mg/kg of 5‐AC were injected intraperitoneally into pregnant rats on day 13 of gestation. The susceptibility order of each digit was the second > third > first > fourth > fifth in the forepaw and the second > first > third ė fourth > fifth in the hindpaw. In the forepaw, the percentages of cutaneous syndactyly with closely apposed metacarpals or osseous syndactyly between the first and second digits (type FA defect) and brachydactyly of the third digit (type FB defect) were increased in a clear dose‐related trend. In the hindlimb, the percentages of osseous or cutaneous syndactyly between the first and second digits (type HA defect), brachydactyly or ametatarsia of the second digit (type HB defect), and osseous or cutaneous syndactyly, closely apposed metacarpals, lateral metacarpal fusion, or osseous or cutaneous syndactyly with lateral metacarpal fusion or closely apposed metacarpals between the third and fourth digits (type HC defect) reached a maximum at 0.7 mg/kg of 5‐AC and then decreased. However, the percentages of ectrodactyly, 1 missing digit (type M1 defect) or 2 missing digits (type M2 defect), were increased from 0.6 mg/kg or 0.7 mg/kg, respectively. Ectrodactyly, missing 3 digits (type M3 defect), was rarely observed in the dose range used.