chapter  6
4 Pages


WithJames L. Schardein, Orest T. Macina

Mechlorethamine is an alkylating antineoplastic drug that has therapeutic utility in combination therapy for Hodgkin’s disease and non-Hodgkin’s lymphoma and other malignant lymphomas. The drug inhibits DNA and RNA synthesis via formation of carbonium ions by cross-linking strands of DNA, causing miscoding, breakage, and failure of replication. The drug has been associated with congenital malformation in the human as well. The malformations recorded are diverse, having similarities in two cases with digit abnormalities and three with brain defects. The digit defects were similar to some recorded animal malformations. Malformations were accompanied by dysmaturity in one case and learning disability in a single case, neither of which are considered significant biological effects in the developmental toxicity parameter of this agent. Death or abortion occurred in the majority of the cases and was considered an associated feature of the developmental toxicity profile of mechlorethamine.