Document Detail


The effect on the Km for radiosensitization at 0 degree C of thiol depletion by diethylmaleate pretreatment: quantitative differences found using the radiation sensitizing agent misonidazole or oxygen.
MedLine Citation:
PMID:  6718689     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Pretreatment of V79- WNRE cells with 150 microM diethylmaleate for 1 hr at 37 degrees C caused a decrease in intracellular glutathione levels to approximately 10-15% of control levels (0.5 vs 5.0 nmol/10(6) cells). The cells could be washed free of diethylmaleate and held at 0 degree 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 Km of about sevenfold from 0.6 to 0.09 mM. In contrast, only a 2.5-fold decrease was found in the Km 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.
Authors:
C J Koch; C C Stobbe; E A Bump
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Radiation research     Volume:  98     ISSN:  0033-7587     ISO Abbreviation:  Radiat. Res.     Publication Date:  1984 Apr 
Date Detail:
Created Date:  1984-06-20     Completed Date:  1984-06-20     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0401245     Medline TA:  Radiat Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  141-53     Citation Subset:  IM; S    
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Survival / drug effects,  radiation effects*
Cells, Cultured / drug effects
Cesium Radioisotopes
Cricetinae
Cricetulus
Dose-Response Relationship, Drug
Dose-Response Relationship, Radiation
Gamma Rays
Glutathione / physiology*
Maleates / pharmacology
Misonidazole / pharmacology*
Nitroimidazoles / pharmacology*
Oxygen / pharmacology*
Radiation-Sensitizing Agents / pharmacology*
Chemical
Reg. No./Substance:
0/Cesium Radioisotopes; 0/Maleates; 0/Nitroimidazoles; 0/Radiation-Sensitizing Agents; 13551-87-6/Misonidazole; 141-05-9/diethyl maleate; 70-18-8/Glutathione; 7782-44-7/Oxygen

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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