Drug selectivity and membrane transport properties of normal human lymphocytes.
This study used Interleukin (IL)-stimulated normal human lymphocytes in culture as a model system to examine membrane transport systems and drug cytotoxicity. Normal peripheral blood mononuclear cells were stimulated with either purified IL-1 or phytohemagglutinin (PHA) and maintained for several months in IL-2. Only 'T' lymphocytes grew in culture. Amino acid transport was compared in PHA-stimulated cells and IL-stimulated cells. Both the PHA- and IL-stimulated lymphocyte cell lines had similar generation times and similar uptake and efflux of cisplatin and methotrexate. Yet, PHA-stimulated cells proved 3- to 5-fold more sensitive to the cytotoxic effects of these drugs. The greater drug sensitivity of the PHA-stimulated cell line was associated with enhanced sodium-dependent methionine transport and altered amino acid transport systems. Differences in the nutrient transport systems are comparable to those previously observed between drug sensitive and resistant cells, and may provide the biochemical basis for cisplatin and methotrexate collateral resistance.
Kashani-Sabet
M
M
Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, Duarte, Calif.
Scanlon
K J
KJ
D000596:Amino Acids / Q000493:pharmacokinetics; D001692:Biological Transport / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D002945:Cisplatin / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D008213:Lymphocyte Activation; D008727:Methotrexate / Q000493:pharmacokinetics / Q000494:pharmacology*; D010835:Phytohemagglutinins / Q000494:pharmacology; D012964:Sodium / Q000494:pharmacology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D000596:Amino Acids; D007375:Interleukin-1; D010835:Phytohemagglutinins; D012964:Sodium; D002945:Cisplatin; D008727:Methotrexate