Metabolic activation of cyclophosphamide by yolk sac endodermal cells of the early chick embryo

Endodermal cells isolated from the yolk sacs of day 3 chick embryos were able to activate metabolically cyclophosphamide. This was demonstrated by the cytotoxicity of cyclophosphamide to the endodermal cells themselves as well as by the ability of endodermal tissue to mediate a cytotoxic response in coculture with KB cells, a human tumor cell line unable to activate cyclophosphamide. Yolk sac endodermal cells from day 3 embryos were sensitive to cyclophosphamide when the drug was added immediately after the start of culture, but not when the drug was added after 24 hr of culture. The ability to metabolize cyclophosphamide by the day 3 embryo appeared limited to the endodermal cells of the yolk sac as cells derived from neither the embryo proper nor yolk sac mesoderm-ectoderm tissue were positive in these tests. Using whole blastoderms, cyclophosphamide activation was detected as early as 12 hr of egg incubation.