TERATOGENIC BIOACTIVATION OF CYCLOPHOSPHAMIDE INVITRO

Day 10 rat embryos grown as cultured explants in vitro developed characteristic defects when culture media contained cyclophosphamide (6.25 .mu./ml or more), an hepatic microsomal fraction and cofactors for a monooxygenase system. Cyclophosphamide concentrations as high as 250 .mu./ml were innocuous when either the microsomal material or cofactors were omitted from the medium. These experiments represent the 1st direct demonstration of bioactivation of a proteratogen.