Circadian modification of 5-fluorouracil-induced teratogenesis in mice

Pregnant mice were treated intraperitoneally with 5-fluorouracil in a single dose of 30 mg/kg once on gestation day 11 at one of four selected times along the 24-hr time scale. All animals were kept under a lighting regimen of 12 hr (0600-1800) alternating with 12 hr of darkness. They were injected at the same circadian phase as they were mated. The developmental age of all fetuses was 264 +/- 1 hr at the time of injection. Fetuses collected on day 18 showed a circadian variation in teratogenic susceptibility to 5-fluorouracil. The lethal and teratogenic risk posed by the drug were highest among animals treated at the mid-light period until the onset of darkness.