This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Lyons, R. M. Articles by Goldenberg, G. J. Search for Related Content PubMed PubMed Citation Articles by Lyons, R. M. Articles by Goldenberg, G. J.

Active Transport of Nitrogen Mustard and Choline by Normal and Leukemic Human Lymphoid Cells¹

Department of Medicine, University of Manitoba and The Manitoba Institute of Cell Biology, Winnipeg, Manitoba, R3E OV9, Canada

Transport of hydrolyzed nitrogen mustard (HN2-OH) and choline by human lymphoid cells was investigated in normal individuals and in patients with chronic lymphocytic leukemia or acute lymphoblastic leukemia. Uptake of HN2-OH-¹⁴C and choline-¹⁴C by normal and leukemic cells proceeded "uphill" against a concentration gradient, was temperature dependent, followed Michaelis-Menten kinetics, and demonstrated chemical specificity, thus suggesting that transport was an active, carrier-mediated process. The transport K_m for both substrates was lowest in acute lymphoblastic leukemia lymphoblasts, suggesting that those cells showed the greatest affinity between carrier site and substrate. Transport capacity as measured by V_max was also greatest in acute lymphoblastic leukemia lymphoblasts, indicating a larger number of transport sites and/or faster carrier mobility. Certain inconsistencies in HN2-OH and choline transport suggested that more than a single, common transport system was involved. Discrepancies between K_m and K_i suggested that HN2-OH was a more efficient inhibitor of choline transport and, conversely, that choline was a less efficient inhibitor of HN2-OH transport than would be expected from their K_m values. HN2-OH acting as inhibitor completely blocked active transport of choline; however, in the reciprocal experiment, choline, even at concentrations 500-fold greater than that of HN2-OH, failed to eliminate active drug transport. HN2-OH uptake examined over a 100-fold range in drug concentration was clearly biphasic. From these findings, at least two components of HN2-OH transport may be postulated, a low-affinity, high-capacity system at "high" drug concentrations and a high-affinity, low-capacity system that appears to be shared with choline at "low" drug concentrations.

¹ This work was supported by a grant from the National Cancer Institute of Canada.

² Research Fellow of the National Cancer Institute of Canada.

³ Clinical Research Associate of the National Cancer Institute of Canada.

Received 3/10/72. Accepted 4/20/72.