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  • Title: Amino acid-conferred resistance to melphalan. I. Structure-activity relationship in cultured murine L1210 leukemia cells.
    Author: Vistica DT, Toal JN, Rabinovitz M.
    Journal: Cancer Treat Rep; 1976 Sep; 60(9):1363-7. PubMed ID: 1016969.
    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 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. These results are interpreted to suggest that melphalan transport by the L1210 leukemia cell is mediated by a system also responsible for the transport of glutamine and leucine and that interaction with such a system may play a significant role in the chemotherapeutic activity of this alkylating agent.
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