The Effect on the K<sub> m</sub> for Radiosensitization at 0°C of Thiol Depletion by Diethylmaleate Pretreatment: Quantitative Differences Found Using the Radiation Sensitizing Agent Misonidazole or Oxygen
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Medientyp:
E-Artikel
Titel:
The Effect on the K<sub> m</sub> for Radiosensitization at 0°C of Thiol Depletion by Diethylmaleate Pretreatment: Quantitative Differences Found Using the Radiation Sensitizing Agent Misonidazole or Oxygen
Beteiligte:
Koch, C. J.;
Stobbe, C. C.;
Bump, E. A.
Erschienen:
Academic Press, Inc., 1984
Erschienen in:
Radiation Research, 98 (1984) 1, Seite 141-153
Sprache:
Englisch
ISSN:
0033-7587;
1938-5404
Entstehung:
Anmerkungen:
Beschreibung:
<p> Pretreatment of V79-WNRE cells with 150 μM diethylmaleate for 1 hr at 37°C caused a decrease in intracellular glutathione levels to approximately 10-15% of control levels (0.5 vs <tex-math>$5.0\ {\rm nmol}/10^{6}\ \text{cells}$</tex-math>). The cells could be washed free of diethylmaleate and held at 0°C for several hours without toxicity and with no increase in glutathione concentration, although the glutathione concentration rapidly increased to normal levels at higher temperatures. Survival curves were determined as a function of oxygen or misonidazole concentration (the latter in the absence of oxygen). A new "thin-film" technique was used to avoid changes in oxygen concentration because of radiochemical or cellular oxygen consumption. Glutathione depletion itself caused a small but consistent radiosensitization of hypoxic cells (dose enhancement ratio of 1.2). However, glutathione depletion caused a profound change in the radiosensitizing efficiency of misonidazole, with a decrease in K<sub> m</sub> of about sevenfold from 0.6 to 0.09 mM. In contrast, only a 2.5-fold decrease was found in the K<sub> m</sub> for radiosensitization by oxygen with diethylmaleate pretreatment. These results suggest a fundamental problem with the conventional theory of radiosensitivity whereby one considers a first-order competition for reaction with target radicals between radical-fixing versus radical-repairing species. It also suggests difficulties in the interpretation of glutathione as the only endogenous protective species. </p>