CHANGES IN SURVIVAL AND POTENTIALLY LETHAL DAMAGE RECOVERY FOLLOWING PERIODS OF HIGH AND LOW METABOLIC-ACTIVITY IN HUMAN GLIOMA-CELLS

Radiation survival and recovery from potentially lethal damage has bee n measured in human glioblastoma cells as they progressed from an expo nential to an extended plateau growth phase. Immediate plating (IP) su rvival following 7.5 Gy Co-60 irradiation decreased from 2.3% for cell s in exponential growth phase to 0.11 % for cells held in an extended plateau growth phase with no change or adjustments made to the medium. Delayed plating (DP) survival decreased from 10% to 2.5%, respectivel y. Under these conditions, medium pH, rate of glycolysis, and prolifer ation status were monitored. IP survival was found to be sensitive to both proliferation status and the amount of time the cells spent in a metabolically quiescent state. Recovery ratios (DP surv./IP surv.) inc reased from 4.3 to 23, primarily due to IP survival decreasing at a gr eater rate than DP survival. Aerobic glycolysis was found to be respon sible for approximately 42% of the glucose utilization. Metabolic acti vity (glycolysis) was increased by increasing the pH of the existing m edium. Survival was measured 3 days after each pH adjustment to allow a new metabolic equilibrium to establish with a pH and rate of glycoly sis comparable to that in control experiments that had no pH adjustmen ts. Both IP and DP survival showed only slight decreases compared to c ontrol experiments, while the recovery ratio at the end of a 6-day pla teau period remained the same as in control experiments. No additional cell growth or redistribution of cells within the cell cycle occurred . Thus a period of increased metabolic activity prior to irradiation i s advantageous for both IP and DP survival as compared to a period of low metabolic activity. No change occurred in the expression of PLDR e ven though, after several periods of increased glycolysis, minimal glu cose and twice the lactate was present in the medium.