The biochemical and ultrastructural effects of tunicamycin and D-glucosamine in L1210 leukemic cells.
Tunicamycin was found to specifically inhibit the incorporation of a number of sugars into L1210 leukemia cell glycoproteins. This inhibition of glycoprotein biosynthesis led to a cessation of cell growth which was reversible in a dose-dependent and time-dependent manner. After removal of the antibiotic from L1210 cell cultures resumption of sugar incorporation preceded that of thymidine incorporation and the recovery of cell growth. The treatment of cells with tunicamycin resulted in a significant increase in the intracellular pool of UDP-N-acetylglucosamine which occurred concurrently with alterations in cell ultrastructure including distentions of the endoplasmic reticulum and nuclear membranes. Similar ultrastructural changes and increases in the intracellular pools of UDP-sugars were observed in L1210 cells exposed to 5 mM D-glucosamine, which suggested that the antiproliferative effects of tunicamycin may be related to the accumulation in the endoplasmic reticulum of one or more nucleotide sugar precursors of asparagine-linked glycoprotein biosynthesis. However, the biological effects of tunicamycin could be distinguished from those caused by D-glucosamine. Exposure of L1210 cells to tunicamycin resulted in specific alterations in the biochemical composition of the plasma membrane and in the inhibition of cellular agglutination by wheat germ agglutinin which were not apparent following exposure to equitoxic concentrations of the aminosugar. These studies, together with those which demonstrated that recovery of the cellular capacity to synthesize glycoproteins was obligatory for the recovery of cellular proliferation in tunicamycin-treated cells, suggested that inhibition of the synthesis of glycoproteins was the major factor limiting L1210 leukemic cell proliferation.
D000371:Agglutination; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002462:Cell Membrane / Q000032:analysis; D004247:DNA / Q000096:biosynthesis; D004721:Endoplasmic Reticulum / Q000187:drug effects*; D005643:Fucose / Q000378:metabolism; D005944:Glucosamine / Q000494:pharmacology*; D006023:Glycoproteins / Q000096:biosynthesis*; D007939:Leukemia L1210; D008358:Mannose / Q000378:metabolism; D051379:Mice; D009363:Neoplasm Proteins / Q000096:biosynthesis; D009685:Nuclear Envelope / Q000187:drug effects*; D014415:Tunicamycin / Q000494:pharmacology; D014537:Uridine Diphosphate N-Acetylglucosamine / Q000378:metabolism
D006023:Glycoproteins; D009363:Neoplasm Proteins; D014415:Tunicamycin; D005643:Fucose; D014537:Uridine Diphosphate N-Acetylglucosamine; D004247:DNA; D005944:Glucosamine; D008358:Mannose