REDUCTION IN CELL-SURFACE CONCANAVALIN A BINDING AND MANNOSE INCORPORATION INTO GLYCOPROTEINS OF SARCOMA-180 BY 6-THIOGUANINE

Treatment of mice bearing Sarcoma 180 ascites cells with 20 mg kg of 6-thioguanine for 1 hr caused a 50 per cent decrease in [2-3H]mannose incorporation into glycoproteins; this inhibition continued for at least 6 hr after drug exposure. The decrease in labeling of mannose-containing glycoproteins produced by the 6-thiopurine was followed by a decrease in the specific binding of Concanavalin A to Sarcoma 180; this effect was observed as early as 12 hr after 6-thioguanine treatment. The decrease in specific binding of Concanavalin A to Sarcoma 180 24 hr after 6-thioguanine was due to a 20 per cent reduction in the number of Concanavalin A receptors available on the plasma membrane of these neoplastic cells. The binding of lectins specific for sugars not activated by GTP, such as Wheat Germ Agglutinin and Ricinus communis, was not decreased by treatment of cells with the purine antimetabolite. This disruption in the biochemical composition of the cell surface produced by 6-thioguanine was accompanied by morphological alterations in the microvillar content of Sarcoma 180 cells which were observed by scanning electron microscopy. The alterations in membrane composition and structure caused by this antineoplastic agent are hypothesized to be of importance in the delayed cytotoxicity of 6-thioguanine. © 1979.