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 been measured in human glioblastoma cells as they progressed from an exponential to an extended plateau growth phase. Immediate plating (IP) survival following 7.5 Gy 60Co irradiation decreased from 2.3% for cells 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%, respectively. Under these conditions, medium pH, rate of glycolysis, and proliferation 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.) increased from 4.3 to 23, primarily due to IP survival decreasing at a greater rate than DP survival. Aerobic glycolysis was found to be responsible for approximately 42% of the glucose utilization. Metabolic activity (glycolysis) was increased by increasing the pH of the existing medium. Survival was measured 3 days after each pH adjustment to allow a new metabolic equilibrium to establish with a pH and rate of glycolysis comparable to that in control experiments that had no pH adjustments. Both IP and DP survival showed only slight decreases compared to control experiments, while the recovery ratio at the end of a 6-day plateau 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 is advantageous for both IP and DP survival as compared to a period of low metabolic activity.(ABSTRACT TRUNCATED AT 250 WORDS)
Heller
D P
DP
Ottawa Regional Cancer Center, Ontario, Canada.
Feeley
M M
MM
Raaphorst
G P
GP
D002453:Cell Cycle; D002470:Cell Survival / Q000528:radiation effects*; D005910:Glioma / Q000378:metabolism / Q000473:pathology* / Q000532:radiotherapy; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis; D006801:Humans; D006863:Hydrogen-Ion Concentration; D011836:Radiation Tolerance; D014407:Tumor Cells, Cultured
D005947:Glucose