Energy linked modifications of the radiation response in a human cerebral glioma cell line

Effects of cellular energy metabolism on the radiation response of a cell derived from a human cerebral glioma have been studied under conditions of energy limitation produced by the presence of inhibitors of respiratory metabolism (KCN) and glycolysis (glucose analogues such as 2-DG, 5-TG, and 3-0-MG). Radiation 60Co induced DNA repair (Unscheduled DNA Synthesis) and micronuclei formation were studied as measures of radiation response. Glycolysis (lactate production) and levels of adenine and related nucleotides (UTP, GTP, ATP etc.) were measured as parameters of energy metabolism. Two 2-DG (5 mM) inhibited DNA repair and increased micronuclei frequency both in the presence and absence of respiration (KCN, 2 mM). Under similar experimental conditions, the presence of 2-DG also significantly reduced the cellular energy status. Five-TG and 3-0-MG on the other hand, neither significantly altered the energy status (sigma XTP) nor influenced the radiation response under respiratory proficient conditions. The results can be explained on the basis of a model postulating differential energy linked modulations of the repair and fixation processes acting on DNA lesions. Implications of the present results for the radiotherapy of brain tumors are discussed.