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Relationship between intracellular GSH levels and hypoxic cell radiosensitivity.

M B Astor1, M E Anderson, A Meister

  • 1Columbia College of Physicians and Surgeons, Radiological Research Laboratory, New York, New York 10032.

Pharmacology & Therapeutics
|January 1, 1988
PubMed
Summary

Cell plating density influences oxygen enhancement ratio (OER) values. Depleting cysteine and glutathione (GSH) increases radiation sensitivity in hypoxic fibroblasts, but GSH replenishment restores protection.

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Area of Science:

  • Cell biology
  • Radiation oncology
  • Biochemistry

Background:

  • Cellular response to radiation is influenced by oxygen levels and endogenous molecules.
  • Glutathione (GSH) and cysteine play roles in cellular protection against oxidative stress and radiation damage.
  • Oxygen Enhancement Ratio (OER) quantifies the increased biological effectiveness of radiation under aerobic versus hypoxic conditions.

Purpose of the Study:

  • To investigate the impact of cell plating density on OER.
  • To determine the role of cysteine and GSH depletion in radiation sensitivity under varying oxygen conditions.
  • To evaluate the protective effect of GSH repletion against radiation in hypoxic cells.

Main Methods:

  • Experiments were conducted using V79 and GM3877 cell lines.

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  • Cellular GSH and cysteine levels were manipulated through depletion and replenishment.
  • Radiation sensitivity was assessed under both hypoxic and aerobic conditions.
  • Oxygen Enhancement Ratio (OER) was experimentally determined.

    • Main Results:

    • Cell plating density was found to affect experimentally determined OER values.
    • Fibroblasts deficient in cysteine and GSH exhibited heightened sensitivity to radiation under hypoxia.
    • Under aerobic conditions, the absence of cysteine or GSH did not significantly alter radiation sensitivity.
    • Supplementation with Glycine Ethyl Ester (GEE) increased intracellular GSH in depleted V79 cells, conferring protection against hypoxic radiation.

    Conclusions:

    • Cell plating density is a critical factor influencing OER measurements.
    • Cysteine and GSH are essential for protecting cells against radiation-induced damage under hypoxic conditions.
    • Restoring intracellular GSH levels can mitigate radiation sensitivity in cells exposed to hypoxia.