title: Amino acid-conferred resistance to melphalan. I. Structure-activity relationship in cultured murine L1210 leukemia cells.
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.
mesh_terms: D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D004347:Drug Interactions; D004351:Drug Resistance; D005973:Glutamine / Q000378:metabolism / Q000494:pharmacology; D007930:Leucine / Q000378:metabolism / Q000494:pharmacology; D007939:Leukemia L1210 / Q000188:drug therapy*; D008558:Melphalan / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D051379:Mice; D010649:Phenylalanine / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000596:Amino Acids; D005973:Glutamine; D010649:Phenylalanine; D007930:Leucine; D008558:Melphalan