Biomaterial Database

Amino acid-conferred resistance to melphalan. I. Structure-activity relationship in cultured murine L1210 leukemia cells. 1976

D T Vistica, and J N Toal, and M Rabinovitz

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.

UI	MeSH Term	Description	Entries
D007930	Leucine	An essential branched-chain amino acid important for hemoglobin formation.	L-Leucine,Leucine, L-Isomer,L-Isomer Leucine,Leucine, L Isomer
D007939	Leukemia L1210	An experimental LYMPHOCYTIC LEUKEMIA of mice.	Leukemia L 1210,L 1210, Leukemia,L1210, Leukemia
D008558	Melphalan	An alkylating nitrogen mustard that is used as an antineoplastic in the form of the levo isomer - MELPHALAN, the racemic mixture - MERPHALAN, and the dextro isomer - MEDPHALAN; toxic to bone marrow, but little vesicant action; potential carcinogen.	Medphalan,Merphalan,Phenylalanine Mustard,Sarcolysine,Sarkolysin,4-(Bis(2-chloroethyl)amino)phenylalanine,Alkeran,L-PAM,Mustard, Phenylalanine
D010649	Phenylalanine	An essential aromatic amino acid that is a precursor of MELANIN; DOPAMINE; noradrenalin (NOREPINEPHRINE), and THYROXINE.	Endorphenyl,L-Phenylalanine,Phenylalanine, L-Isomer,L-Isomer Phenylalanine,Phenylalanine, L Isomer
D002478	Cells, Cultured	Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.	Cultured Cells,Cell, Cultured,Cultured Cell
D004347	Drug Interactions	The action of a drug that may affect the activity, metabolism, or toxicity of another drug.	Drug Interaction,Interaction, Drug,Interactions, Drug
D004351	Drug Resistance	Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from DRUG TOLERANCE which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration.	Resistance, Drug
D005973	Glutamine	A non-essential amino acid present abundantly throughout the body and is involved in many metabolic processes. It is synthesized from GLUTAMIC ACID and AMMONIA. It is the principal carrier of NITROGEN in the body and is an important energy source for many cells.	D-Glutamine,L-Glutamine,D Glutamine,L Glutamine
D000596	Amino Acids	Organic compounds that generally contain an amino (-NH2) and a carboxyl (-COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins.	Amino Acid,Acid, Amino,Acids, Amino
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia