On the Specific Toxicity of 5-Thio-D-Glucose to Hypoxic Cells

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Abstract
The toxicity of 5-thio-D-glucose (5TG) to mammalian cells [Chinese hamster lung cells] in culture was studied with respect to O2 tension, concentration and temperature. At 37.degree. C and at 5 mM concentration of the drug in normal growth medium, survival is 10-3 for 4-h exposure to 5 ppm O2; this increases to 0.5 for 24-h exposure to 200 ppm [parts/million] O2. The relationship between survival and O2 tension is nonlinear with the greatest change occurring between 50 and 100 ppm. The drug is essentially nontoxic to aerated cells. Drug toxicity increases with concentrations up to about 5 mM at which point a plateau is reached. The effect of elevated temperature is to reduce the time required to obtain a specific level of survival, but temperatures as high as 42.degree. C had only a slight effect on drug toxicity for O2 tensions > 100 ppm. The effect of D-glucose on the toxicity of 5TG was studied, and an inverse relationship was established. At D-glucose concentrations > 20 mM the toxicity of 5TG was nullified regardless of O2 tension or 5TG concentration. [The use of this drug as a radiosensitizer in the X-irradiation of tumor cells is discussed.].