Sensitivity of L5178Y lymphoblasts to the alkylating agent nitrogen mustard (HN2) was found to be a function of the proliferative state of the cells. Dose-survival curves showed that exponential or log-phase cells were 2.6-fold more sensitive to the drug than were stationary-phase cells. Carrier-mediated transport of 14C-labeled HN2, hydrolyzed HN2, and the natural substrate choline was also a function of the proliferative state of the cells. Transport was more efficient in log-phase cells as manifested by a higher binding affinity between carrier and each of the three substrates; in addition transport capacity for hydrolyzed HN2 and choline was significantly greater in log-phase cells than resting cells. The greater sensitivity of log-phase cells to HN2 to a large extent can be accounted for by a more efficient transport mechanism. The activity of the transport system for HN2 may be dependent upon proliferative rate, transport being more active in rapidly dividing cells.


This study was supported by a research grant from the National Cancer Institute of Canada. Presented in a preliminary from at the annual meeting of the Canadian Society for Clinical Investigation, Ottawa, Canada, January 1971 (Clin. Res., 18: 740, 1970).

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