Effect of L-alpha-amino-gamma-guanidinobutyric acid on melphalan therapy of the L1210 murine leukemia.
About half the mice administered a lethal inoculum of L1210 leukemia become 60-day survivors when treated with an appropriate dose of melphalan. Leucine completely abolishes this long-term survival by interfering with melphalan uptake into the tumor cells. L-alpha-Amino-gamma-guanidinobutyric acid, the lower homolog of arginine, promotes melphalan uptake in vitro only in the presence of leucine. When administered to mice with melphalan and a dose of leucine which negates the 50% cure rate of melphalan, it reduces the therapeutic interference of leucine. However, L-alpha-Amino-gamma-guanidinobutyric acid alone does not improve melphalan therapy, suggesting that endogenous leucine can play only a minor role in interference with therapy of the L1210 leukemia.
D000613:Aminobutyrates / Q000494:pharmacology*; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D006146:Guanidines / Q000494:pharmacology; D007930:Leucine / Q000008:administration & dosage; D007939:Leukemia L1210 / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008558:Melphalan / Q000008:administration & dosage* / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains
D000613:Aminobutyrates; D006146:Guanidines; D007930:Leucine; D008558:Melphalan