ANALYSIS OF DIURNAL DIFFERENCE IN TERATOGEN (ARA-C) SUSCEPTIBILITY IN MOUSE EMBRYOS BY A PROGRESSIVE PHASE-SHIFT METHOD

Our objectives were to determine whether the embryotoxic and teratogenic potential of cytosine arabinoside (Ara-C) differs depending on the time of day. Pregnant CD-1 (ICR) mice were placed in an environment where the phases of lighting and darkness was reversed by progressive phase-delay or phase-advance methods.sbd.2 h every day from day of gestation (dg) 2 to dg 7 (or 6). After it was confirmed that these progressive phase-shifting methods had no effect on embryonic growth and pregnancy outcome, 5 mg/kg body weight (bt) of Ara-C was injected intraperitoneally into these animals at 1000 or 1600 on dg 11, and the incidence of gross fetal malformations was compared with that in control dams treated similarly but under a regular lighting regimen (0600-1800). In contrast to previous reports on other teratogens, no diurnal difference was observed in fetal susceptibility to the teratogenic potential of Ara-C. The possible usefulness of the progressive phase-shifting method in the field of chronoteratology is proposed.