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Drug-induced Stimulation of Nitrogen Mustard and Choline Transport and Other Systems in L5178Y Lymphoblasts in Vitro¹

Department of Medicine, University of Manitoba, and The Manitoba Institute of Cell Biology, Winnipeg, Manitoba, Canada, R3E 0V9

The effect of 5 drugs on the transport of several substrates, including the chemotherapeutic agent nitrogen mustard; choline; two nonmetabolizable amino acids, -aminoisobutyric acid and cycloleucine; the glucose analog, 3-O-methyl-D-glucose; and the heme precursor, -aminolevulinic acid; was undertaken in L5178Y murine lymphoblasts in vitro. Transport of both hydrolyzed nitrogen mustard and choline was stimulated by 50 µM atropine, morphine, and cocaine and, in each instance, the results were highly significant (p < 0.001). Conversely, diazepam and phenobarbital had no effect. A kinetic analysis of choline transport in the presence of atropine, morphine, and cocaine revealed primarily an increase in V_max and, to a lesser extent, an increase in K_m.

-Aminoisobutyric acid transport was significantly stimulated (p < 0.01) by cocaine, atropine, and diazepam, but not by morphine or phenobarbital. Transport of the other amino acid, cycloleucine, was stimulated by all 5 drugs, with a maximal effect being obtained with diazepam.

Transport of the sugar 3-O-methyl-D-glucose was also stimulated by all 5 drugs; however, the findings differed from those noted for cycloleucine in that maximal stimulation was observed with cocaine and atropine. Conversely, none of the drugs in this study stimulated -aminolevulinic acid transport. The evidence suggests that drug interactions leading to stimulation of transport systems appear to be complex and, from this initial study, no predictable patterns of stimulation may yet be formulated.

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

² Clinical Research Associate of the National Cancer Institute of Canada.

Received 4/11/74. Accepted 6/20/74.