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Schans, G.P. van der; Vos, O.; Roos-Verheij, W.S.D.; Lohman, P.H.M.
Gezondheidsorganisatie TNO, Rijswijk (Netherlands). Medisch Biologisch Lab1986
Gezondheidsorganisatie TNO, Rijswijk (Netherlands). Medisch Biologisch Lab1986
AbstractAbstract
[en] Treatment of mammalian cells with buthionine sulphoximine (BSO) or diethyl maleate (DEM) results in a decrease in the intracellular GSH (glutathione) and NPSH (non-protein-bound SH) levels. The effect of depletion of GSH and NPSH on radiosensitivity was studied in relation to the concentration of oxygen during irradiation. Single- and double-strand DNA breaks (ssb and dsb) and cell killing were used as criteria for radiation damage. Under aerobic conditions, BSO and DEM treatment gave a small sensitization of 10-20% for the 3 types of radiation damage. Also under severely hypoxic conditions (0.01 μM oxygen in the medium) the sensitizing effect of both compounds on the induction of ssb and dsb and on cell killing was small (0-30%). At somewhat higher concentrations of oxygen (0.5-10 μM) however, the sensitization amounted to about 90% for the induction of ssb and dsb and about 50% for cell killing. These results strengthen the widely accepted idea that intracellular SH-compounds compete with oxygen and other electron-affinic radiosensitizers with respect to reaction with radiation-induced damage, thus preventing the fixation of DNA damages by oxygen. These results imply that the extent to which SH-compounds affect the radiosensitivity of cells in vivo depends strongly on the local concentration of oxygen. (Auth.)
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May 1986; 28 p; Includes Dutch summary; 30 refs.; 6 figs.; 1 table.
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