chapter  1
6 Pages


WithJames L. Schardein, Orest T. Macina

Aminopterin, a formerly used antimetabolite antineoplastic agent for the treatment of acute leukemia in children, has been largely replaced in this category by meth-otrexate, and is used mainly as a rodenticide. Folic acid antagonists like aminopterin that inhibit dihydrofolate result in cell death during the S-phase of the cell cycle. Given to human subjects in the decades of the 1950s through the 1970s, aminopterin was associated with 20 cases of malformation and associated developmental toxicity due to unsuccessful abortion attempts. These cases are of great interest to teratologists and clinicians, for they represent one of the very few teratologic experiments performed in the human. Aminopterin is a large heterocyclic structure that can participate in hydrogen bonding interactions, both as an acceptor and as a donor. It is hydrophilic and has a relatively large polar surface area in comparison to the other human developmental toxicants.