Effects of 2-deoxy-D-glucose on glycolysis, proliferation kinetics and radiation response of human cancer cells.

The effects of 2-deoxy-D-glucose (2-DG) on energy metabolism, cell proliferation kinetics, radiation-induced DNA repair, and micronuclei formation in HeLa cells have been studied. Results show that the 2-DG induced modifications of the radiation effects are biphasic: at high 2-DG concentrations (greater than 2.5 mM), DNA repair is inhibited and manifestation of radiation damage is enhanced as observed by an increase in the radiation (X ray) induced micronuclei formation; lower concentrations of 2-DG (less than 2.5 mM) do not inhibit DNA repair and a decrease in the frequency of micronuclei formation is observed. These data, in correlation with the effects of 2-DG on glycolysis and cell proliferation kinetics, can be explained by the hypothesis that 2-DG induced modifications of radiation effects arise as a result of energy linked differential inhibitions of pathways of repair and fixation of DNA damage. Implications for cancer therapy are discussed.