Subject(s)
Amino Acids/pharmacology , Leucine/pharmacology , Leukemia L1210/drug therapy , Melphalan/pharmacology , Aminobutyrates/pharmacology , Animals , Arginine/analogs & derivatives , Arginine/pharmacology , Cell Survival/drug effects , Cells, Cultured , Culture Media , Drug Antagonism , Guanidines/pharmacology , Leukemia L1210/metabolism , Melphalan/metabolism , Mice , Structure-Activity Relationship , Time FactorsSubject(s)
Amino Acids/pharmacology , Leukemia L1210/metabolism , Melphalan/antagonists & inhibitors , Amino Acids/metabolism , Animals , Biological Transport , Cell Survival/drug effects , Cells, Cultured , Kinetics , Leucine/metabolism , Leukemia L1210/drug therapy , Melphalan/metabolism , Melphalan/pharmacology , MiceABSTRACT
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.
Subject(s)
Amino Acids/pharmacology , Leukemia L1210/drug therapy , Melphalan/pharmacology , Animals , Cells, Cultured , Drug Interactions , Drug Resistance , Glutamine/metabolism , Glutamine/pharmacology , Leucine/metabolism , Leucine/pharmacology , Melphalan/metabolism , Melphalan/toxicity , Mice , Phenylalanine/pharmacology , Structure-Activity RelationshipABSTRACT
A substantial loss of deoxyribonucleic acid-thymine occurs during thymine starvation of several thymine auxotrophs derived from Escherichia coli strains B, 15, and K-12.
