Circadian modification of drug-induced teratogenesis in rat fetuses.
Pregnant Sprague-Dawley rats were injected with hydroxyurea (750 mg/kg) or physiological saline on the 12th day of gestation. Hydroxyurea and saline (control) treated groups were each composed of six subgroups injected at consecutive 4-h intervals (i.e., group 1 at 00(00), group 2 at 04(00),...). All females were injected at the same circadian phase as they were mated. The developmental age of all fetuses was 288 +/- 2 hrs at the time of injection. The fetuses were taken by caesarean section on the 20th or 21st day of gestation. Teratogenesis was greatest when hydroxyurea was administered in the light phase (light-dark 12:12 cycle). Deformity rates correlate with motor activity, mitotic rates and DNA synthesis.
Abnormalities, Drug-Induced↗