Relationship between DNA repair and cell recovery: Importance of competing biochemical and metabolic processes

Ankeren, S. C. van; Wheeler, Kenneth T.

doi:10.1007/bf01210934

Cited by 11 publications

(1 citation statement)

References 29 publications

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“…It was suggested that perhaps error-prone or error-free repair is predominant in conditions that prevent or promote PLDR, respectively . It has been suggested that imbalances in sets of competing biochemical or metabolic processes postirradiation determines survival rather than the presence of a single class of unrepaired DNA lesions (van Ankeren andWheeler 1985, Wheeler et al . 1992) .…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Potentially Lethal Damage Recovery by Altered PH, Glucose Utilization and Proliferation in Plateau Growth Phase Human Glioma Cells

Heller

Raaphorst

1994

International Journal of Radiation Biology

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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.

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Section: Discussionmentioning

confidence: 99%

Inhibition of Potentially Lethal Damage Recovery by Altered PH, Glucose Utilization and Proliferation in Plateau Growth Phase Human Glioma Cells

Heller

Raaphorst

1994

International Journal of Radiation Biology

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Radiation-induced cytotoxicity, DNA damage and DNA repair: Implications for cell survival theory

Swarts

Nelson

Wallen

et al. 1990

Radiat Environ Biophys

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The radiosensitivities and the kinetics for removal of radiation-induced DNA damage were compared for proliferative (P) and quiescent (Q) cells of the lines 66 and 67 derived from a mouse mammary adenocarcinoma. As determined from cell survival assays, the 66 and 67 Q cells were more radiosensitive than their 66 and 67 P counterparts. The rank order of their radiosensitivity was: 67 Q greater than 66 Q greater than or equal to 67 P greater than 66 P. Induction of radiation damage in the DNA of these cells, as measured by the alkaline elution technique, was identical for 66 and 67 P and Q cells. The repair of this DNA damage was biphasic for 66 and 67 P and Q cells. The half-times for the fast and slow repair phases in 66 Q cells were identical to those previously measured in 67 Q cells. The half-times of the fast and slow repair phases in 66 P cells were also identical to those previously measured in 67 P cells. However, the half-times for the fast and slow repair phases in 66 and 67 Q cells were longer than those measured in their 66 and 67 P counterparts. The 66 cell data are consistent with our previously published hypothesis that Q cells are more radiosensitive than their corresponding P cells because they repair their radiation-induced DNA damage slower. However, our results are not consistent with hypotheses that attempt to explain the radiosensitivity differences between lines 66 and 67 solely on the basis of measurable induction and repair of DNA damage.

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Relationship between DNA damage, DNA repair, metabolic state and cell lethality

Wheeler

Hickman

Nelson

et al. 1992

Radiat Environ Biophys

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Induction of unrepairable DNA damage, accumulation of misrepaired DNA damage, and generation of imbalances in competing biochemical and/or metabolic processes have been proposed to explain the relationship between radiation-induced DNA damage and cell lethality. Theoretically, the temperature dependence of the critical DNA repair process(es) should be 1) either independent of or identical to the temperature dependence of cell killing if the first two hypotheses are correct, and 2) different if the third hypothesis is correct. To test this, exponentially growing rat 9L brain tumor cells were left at 37 degrees C or equilibrated for 3-14 h at 20 degrees C before irradiation. Cells were irradiated and allowed to repair at either 20 degrees C or 37 degrees C. Alternatively, the cells were irradiated at one of these temperatures and immediately shifted to the other temperature for repair. DNA damage was assessed by the alkaline elution technique; cell kill was assessed by a clonogenic assay. 9L cells maintained at 20 degrees C or 37 degrees C sustained the same amount of DNA damage as measured by alkaline elution. DNA repair instantaneously assumed the rate characteristic of the postirradiation temperature. For 9L cells equilibrated, irradiated, and repaired at 20 degrees C, the half-time of the fast phase of the DNA repair decreased by a factor of approximately 2 and the half-time of the slow phase decreased by a factor of approximately 5 over that measured in cells incubated, irradiated and repaired at 37 degrees C. Although the rate of DNA repair decreased substantially at 20 degrees C, the survival of 9L cells that were equilibrated and irradiated at 20 degrees C was greater (p less than 10(-4)) than those incubated and irradiated at 37 degrees C, when assayed by an immediate plating protocol. In addition, the survival of 9L cells equilibrated and irradiated at 20 degrees C and then shifted to 37 degrees C immediately after irradiation was greater (p less than 10(-2)) than that obtained with any other delayed plating protocol. Thus, the temperature dependence of the DNA repair processes measured by alkaline elution was different from the temperature dependence of cell killing measured either by an immediate or delayed plating protocol. These data support the hypothesis that many irradiated 9L tumor cells die because of imbalances in sets of competing biochemical and/or metabolic processes.

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Relationship between DNA repair and cell recovery: Importance of competing biochemical and metabolic processes

Cited by 11 publications

References 29 publications

Inhibition of Potentially Lethal Damage Recovery by Altered PH, Glucose Utilization and Proliferation in Plateau Growth Phase Human Glioma Cells

Inhibition of Potentially Lethal Damage Recovery by Altered PH, Glucose Utilization and Proliferation in Plateau Growth Phase Human Glioma Cells

Radiation-induced cytotoxicity, DNA damage and DNA repair: Implications for cell survival theory

Relationship between DNA damage, DNA repair, metabolic state and cell lethality

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