Changes in glycosylation of L1210 cells after exposure to various antimetabolites.
This study establishes that antimetabolites do have the potency to change cellular glycosylation, as was suggested in our previous review (Eur J Cancer 1990, 26, 516-523). Murine leukaemia L1210 cells were exposed to various antimetabolites under non-lethal conditions. The antimetabolites 5-fluorouracil (5FU), arabinofuranosylcytosine (AraC), methotrexate (MTX) and 6-mercaptopurine (6MP), but not 6-thioguanine, induced considerable changes in the metabolic incorporation of radioactively labelled monosaccharides. Each antimetabolite exhibited a different effect. Significant differences were found between the radioactivity incorporated from the monosaccharides glucosamine, fucose, mannose and galactose, relative to control values. Polyacrylamide gel electrophoresis indicated that changes were induced in the glycosylation of individual glycoproteins. 5FU, AraC, MTX and 6MP all influenced both pyrimidine- and purine-mediated sugar incorporation. This excludes, therefore, direct effects of the antimetabolites on their analogue nucleotide-sugars. The antimetabolite-induced changes in glycosylation did not directly correlate with the observed cell-cycle effects of the antimetabolites.
Department of Medical Chemistry, Faculty of Medicine, Vrije Universiteit, Amsterdam, The Netherlands.
T W
TW
De Graaf
S S
SS
Slot
G J
GJ
Peters
W
W
Van Dijk
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D006023:Glycoproteins / Q000096:biosynthesis; D006031:Glycosylation / Q000187:drug effects; D007939:Leukemia L1210 / Q000378:metabolism*; D051379:Mice; D008938:Mitosis / Q000187:drug effects; D009005:Monosaccharides / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000964:Antimetabolites, Antineoplastic; D006023:Glycoproteins; D009005:Monosaccharides