A comparison of mutagenic and embryotoxic effects of cyclophosphamide on the chick embryo

The cytogenetic and embryotoxic effects of cyclophosphamide (CP) after injection on day 3 of single doses ranging from 0.1 to 30 micrograms were investigated in the chick embryo. The occurrence of embryotoxicity was checked on incubation day 8; clastogenic effects as well as mitotic indices were evaluated in primitive blood cells 6, 12, 18, 24 and 30 hr after the administration of CP. Teratogenic doses of CP induced high percentages of aberrant cells with many unstable aberrations. Mitotic activity appeared to be inhibited at the early collection intervals. Nonembryotoxic doses of CP also increased the incidence of aberrant cells without any substantial effect upon mitotic activity. Although the clastogenic effects of CP occur at lower doses than the teratogenic effects, the thresholds for both effects lie in the lower part of the embryotoxicity dose range, as estimated by the Chick Embryotoxicity Screening Test (CHEST).