Effects of ethanolamine and choline on thiotepa cellular accumulation and cytotoxicity in L1210 cells

Journal Article · Sun Jul 15 00:00:00 EDT 1990 · Cancer Research; (USA)

OSTI ID:6580111

Egorin, M J; Snyder, S W; Wietharn, B E ^[1]

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1. Univ. of Maryland Cancer Center, Baltimore (USA)

The amino alcohols, ethanolamine and choline, were studied for their effects on (a) L1210 cell growth, (b) N,N{prime},N{double prime}-triethylenetheiphosphoramide (thiotepa)-induced growth inhibition of L1210 cells, and (c) 14C accumulation by L1210 cells incubated with (14C)thiotepa. Ethanolamine, at concentrations up to 300 microM, had no effect on L1210 cell growth but, at concentrations greater than 300 microM, 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 microM, nor choline, at 10 mM, altered the ability of thiotepa to reduce L1210 cell growth. Neither ethanolamine, at 250 microM, 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 5 microM (14C)thiotepa, a process which is 80-85% due to production of (14C)phosphatidylethanolamine, was not affected by 250 microM 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 microM 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.

• OSTI ID: 6580111
• Journal Information: Cancer Research; (USA), Vol. 50:14; ISSN 0008-5472
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
62 RADIOLOGY AND NUCLEAR MEDICINE
AMINES
BIOLOGICAL EFFECTS
CHOLINE
TUMOR CELLS
GROWTH
AMIDES
CARBON 14 COMPOUNDS
DOSE-RESPONSE RELATIONSHIPS
ISOTOPE DILUTION
LEUKEMIA
MICE
SURVIVAL TIME
TRACER TECHNIQUES
ALCOHOLS
AMMONIUM COMPOUNDS
ANIMAL CELLS
ANIMALS
DISEASES
DRUGS
HEMIC DISEASES
HYDROXY COMPOUNDS
IMMUNE SYSTEM DISEASES
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LIPOTROPIC FACTORS
MAMMALS
NEOPLASMS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
QUATERNARY COMPOUNDS
RODENTS
VERTEBRATES
550901* - Pathology- Tracer Techniques
550600 - Medicine