Uptake of melphalan by human ovarian carcinoma cells and its relationship to the amino acid content of ascitic fluid.

Melphalan uptake by human ovarian carcinoma cells obtained from patients with clinically documented disease was significantly reduced by ascitic fluid. Examination of the ascitic fluid revealed physiologic concentrations of a number of amino acids, notably leucine (100-150 microM) and glutamine (500-600 microM). These two amino acids, when used at concentrations found in the ascitic fluid, significantly reduced melphalan uptake to levels which approximated those obtained with ascitic fluid. The possible effect of high concentrations of these amino acids on melphalan therapy for this neoplasm is discussed with particular reference to the model melphalan transport system in the murine L1210 leukemia cell. Specific emphasis is placed on the rationale for combining melphalan with arginine and a glutamine-depleting enzyme.