Inhibition of potentially lethal damage recovery by altered pH, glucose utilization and proliferation in plateau growth phase human glioma cells.
Recovery from potentially lethal damage (PLD) has been measured in plateau growth phase human glioblastoma cells (U-87MG) under four postirradiation medium conditions. Recovery was maximal in depleted medium at an acidic pH, conditions which inhibit cellular proliferation. Compared with this control, PLD recovery (PLDR) was increasingly inhibited by alkalization of the existing medium (to pH 7.4), exchanging the old medium with fresh medium-pH acidified (to pH 6.8), and exchanging the old medium with fresh medium-pH unaltered (pH 7.4), respectively. These three medium adjustments were made at the time of irradiation. Increased glucose utilization (glycolysis) was detected postirradiation in all three cases, while increased proliferation was detected only when fresh medium was exchanged for old medium. Thus inhibition of PLDR has been correlated with increased glycolysis and increased proliferation during the recovery period. When acting together, these two processes provided almost complete inhibition. This study was revealed that the degree of inhibition may be related to the amount of glycolysis and/or proliferation occurring during the recovery period. Examining, in vitro, the range of PLDR achieved by postirradiation manipulation of medium pH may provide some indication of the range in PLDR that may be expected in vivo. Our study demonstrates that the effect of pH on glycolysis and proliferation may be important when determining the ability of a particular cell type to recover from PLD.
Heller
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DP
Ottawa Regional Cancer Center, Ontario, Canada.
Raaphorst
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GP
D002455:Cell Division; D002470:Cell Survival; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects*; D011836:Radiation Tolerance; D014407:Tumor Cells, Cultured
D005947:Glucose