Action of three nitrosoureas on human lymphocytes. Hypothesis of a specific effect on lymphocyte subpopulations.
RFCNU [(chloro-2-ethyl)-1-(ribofuranosylisopropylidene-2',3'-paranitrobenzoate-5')-3- nitrosourea], RPCNU [(chloro-2-ethyl)-1-(ribopyranosyltriacetate-2',3',4')-3-nitrosourea] and CCNU [(chloro-2-ethyl)-1-cyclohexyl-3-nitrosourea) were found cytotoxic in vitro for human blood lymphocytes from healthy donors at doses higher than 50 micrograms/ml. Blood lymphocytes from different individuals displayed different behaviors both in their sensitivity to nitrosoureas and in their proliferative response to mitogenic lectins. With pokeweed-mitogen-stimulated lymphocytes the main effect of all three drugs (10 micrograms/ml) was an increase of [3H]-thymidine uptake. This facilitation effect was found only in half of the experiments with phytohemagglutinin-stimulated lymphocytes, while the stimulation by concanavalin A was inhibited under the same conditions. The hypothesis that nitrosoureas might be selectively cytotoxic for a suppressor cell subpopulation might explain the observed increase of thymidine uptake.
D000328:Adult; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008130:Lomustine / Q000494:pharmacology; D008214:Lymphocytes / Q000187:drug effects*; D008297:Male; D008934:Mitogens / Q000494:pharmacology; D009607:Nitrosourea Compounds / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism
D008934:Mitogens; D009607:Nitrosourea Compounds; C023479:ICIG 1163; C015747:RFCNU; D008130:Lomustine; D013936:Thymidine