The use of cultured rat embryos to evaluate the teratogenic activity of serum: Cadmium and cyclophosphamide

Head fold stage rat embryos were cultured for 48 hours in vitro on serum taken at various intervals from rats that had been injected ip with either cadmium or cyclophosphamide. Their response was compared to that of embryos cultured for the same period on control serum to which these substances were added directly. One and 4 hour sera from cadmium-injected rats (2.13 mgCd++/kg) were lethal. Eight hour serum allowed survival but embryos were exencephalic and contained reduced amounts of protein and DNA. The response to direct cadmium was characteristically different and was related to dosage and the extent to which zero-time embryos had progressed through the head fold stage. At 1.6 micro M, Cd++ susceptible embryos were hemorrhagic, though not exencephalic. One hour serum from rats given cyclophosphamide (180 mg/kg) was lethal. On 4 hour serum, embryos survived but were exencephalic and contained less protein and DNA than controls. Embryos were resistant to direct cyclophosphamide up to 800 micrograms per ml of medium. At this concentration, embryos appeared morphologically normal but contained reduced amounts of protein.