Elimination of Hypoxic Protection by 5-Thio-d-glucose in Multicell Spheroids¹

The effect of 5-thio-d-glucose on oxic and hypoxic V79-171 Chinese hamster cells was studied in vitro with single cells and multicell spheroids. At concentrations that were not toxic to oxic cells, this compound killed hypoxic cells with a D₀ of 1 hr with a 5 mm concentration and more rapidly at 10 mm beginning 2 hr after incubation at 37°. 5-Thio-d-glucose also sensitized hypoxic cells to radiation and protected oxic cells from radiation damage. Multicell spheroids irradiated after incubation with the compound demonstrated increased radiosensitivity, although the relative contribution of cytotoxicity and hypoxic cell sensitization could not be evaluated. Spheroid reoxygenation by decreased cell respiration was determined not to be a contributing factor, suggesting that the spheroid-sensitizing effect was due to drug effects on hypoxic cells. The dramatic increase in multicell spheroid radiosensitivity that resulted from treatment with 5-thio-d-glucose suggests that this compound may be used to increase the effectiveness of radiotherapy by eliminating hypoxic protection.