The amino alcohols, ethanolamine and choline, were studied for their effects on (a) L1210 cell growth, (b) N,N′,N″-triethylenethiophosphoramide (thiotepa)-induced growth inhibition of L1210 cells, and (c) 14C accumulation by L1210 cells incubated with [14C]thiotepa. Ethanolamine, at concentrations up to 300 µm, had no effect on L1210 cell growth but, at concentrations > 300 µm, produced a dose-dependent reduction in cell growth. Choline, at concentrations up to 20 mm, had no effect on L1210 cell growth. Neither ethanolamine, at 250 µm, nor choline, at 10 mm, altered the ability of thiotepa to reduce L1210 cell growth. Neither ethanolamine, at 250 µm, nor choline, at 10 mm, affected the rapid phase of 14C accumulation by L1210 cells incubated with [14C]thiotepa. The slow phase of 14C accumulation by L1210 cells incubated with 5µm [14C] thiotepa, a process which is 80–85% due to production of [14C]phosphatidylethanolamine, was not affected by 250 µm choline. In contrast, ethanolamine produced a dose-dependent reduction in this slow rate of 14C accumulation. The reduction in the slow rate of 14C accumulation produced by ethanolamine was due almost entirely to a decrease in the accumulation of nonexchangeable 14C. Kinetic analysis of the inhibition of 14C accumulation produced by 25, 100, and 250 µm ethanolamine was compatible with competitive inhibition. Thin layer chromatography of cell extracts showed that the ability of ethanolamine to reduce 14C accumulation by L1210 cells incubated with [14C]thiotepa was due solely to reduction in production of [14C]phosphatidylethanolamine. These results are all compatible with and predicted by our previously described scheme wherein thiotepa enters cells by simple diffusion and serves as a prodrug for aziridine, some of which is hydrolyzed to ethanolamine which is then incorporated into phosphatidylethanolamine via normal metabolic synthetic pathways.

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