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Glutathione pool size affects cell survival after hyperthermic treatment
M L Freeman1, A W Malcolm, M J Meredith
1Vanderbilt Center for Radiation Oncology, Vanderbilt University, Nashville, TN 37232.
Cell Biology and Toxicology
|June 1, 1985
Summary
Chinese hamster ovary cells
Area of Science:
- Cellular Biology
- Biochemistry
- Radiation Oncology
Background:
- Intracellular glutathione (GSH) plays a crucial role in cellular defense mechanisms.
- GSH is involved in protecting cells against oxidative stress and toxic damage.
- Understanding GSH's role in thermal toxicity is important for cancer therapy.
Purpose of the Study:
- To investigate the relationship between intracellular glutathione (GSH) concentrations and thermal toxicity in Chinese hamster ovary (CHO) cells.
- To determine the effect of varying GSH levels on cellular sensitivity to heat treatment.
- To elucidate the stepwise manner in which GSH regulates thermal toxicity.
Main Methods:
- Chinese hamster ovary (CHO) cells were exposed to varying concentrations of diethylmaleate (DEM) to deplete intracellular glutathione (GSH).
- Steady-state GSH levels were maintained throughout the experiment.
- Cells were subjected to heat treatment at 42°C, and thermal dose response curves were generated using colony formation as the endpoint.
- The slope of the dose-response curve was analyzed in relation to intracellular GSH concentrations.
Main Results:
- Removal of 50% or less of intracellular GSH did not significantly alter thermal sensitivity.
- A moderate increase in thermal sensitivity was observed when 50% to 80% of GSH was depleted.
- Significant increases in thermal toxicity were noted upon removal of greater than 80% of intracellular GSH.
- Low concentrations of DEM (10-20 μM) caused extensive GSH depletion with minimal impact on cell survival, suggesting a GSH threshold effect.
Conclusions:
- Intracellular glutathione (GSH) acts as a critical regulator of thermal toxicity in CHO cells.
- CHO cells possess multiple GSH reservoirs that influence thermal sensitivity in a stepwise manner.
- A threshold level of GSH depletion is required to significantly increase cellular sensitivity to heat stress.
- These findings have implications for optimizing hyperthermia treatments in conjunction with chemotherapy or radiation therapy.