AMINO ACID CONFERRED RESISTANCE TO MELPHALAN .1. STRUCTURE-ACTIVITY RELATIONSHIP IN CULTURED MURINE L1210 LEUKEMIA-CELLS

  • 1 January 1976
    • journal article
    • research article
    • Vol. 60  (9) , 1363-1367
Abstract
Melphalan cytotoxicity to murine L1210 leukemia cells in culture was reduced in growth medium containing amino acids. Investigation of the effect of single amino acids revealed that the L-isomers of glutamine and leucine, but not the D-isomers, were the most active in decreasing cytotoxicity. Protection was concentration dependent, with maximum protection occurring at approximately 0.25 mM, a physiologic concentration. The LD90 [90% lethal dose] for melphalan in the presence of 0.1-mM L-glutamine or L-leucine was increased by 7.3- and 10.8-fold, respectively, under conditions where the cells had been pre-incubated with the amino acids. Melphalan transport by the L1210 leukemia cell may be mediated by a system also responsible for the transport of glutamine and leucine and interaction with such a system may play a significant role in the chemotherapeutic activity of this alkylating agent.