Cytotoxicity as an indicator for transport mechanism: evidence that murine bone marrow progenitor cells lack a high-affinity leucine carrier that transports melphalan in murine L1210 leukemia cells.
Cytotoxicity of melphalan to murine L1210 leukemia cells was reduced to a limiting maximum value of 50% by 2-aminobicyclo[2,2,1]heptane-2-carboxylic acid (BCH), indicating that cytotoxicity is partially dependent on drug uptake by system L. L-Leucine, but not alpha-aminoisobutyric acid (AIB), completely reduced the remaining 50% of drug cytotoxicity. These results contrast with those obtained with a sensitive host tissue, the bone marow progenitor cells of the white cell series (CFU-C), in that a high-affinity leucine transport system corresponding to system L was not identified.
D000621:Aminoisobutyric Acids / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport; D004305:Dose-Response Relationship, Drug; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D007930:Leucine / Q000378:metabolism*; D007939:Leukemia L1210 / Q000378:metabolism*; D008297:Male; D008558:Melphalan / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice
D000621:Aminoisobutyric Acids; D007930:Leucine; D008558:Melphalan