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.

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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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