Endogenous versus exogenous thiols in radioprotection.
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Animals↗
Biomedical subjects
W S Roos-Verhey
Publications and source records attributed to W S Roos-Verhey.
Radioprotection by glutathione esters and cysteamine in normal and glutathione-depleted mammalian cells.
Monoethyl (MEE) and diethyl (DEE) esters of glutathione (GSH) had the capacity to provide some protection of normal and buthionine sulfoximine (BSO) pretreated cells against X-irradiation. Both compounds appeared to be transported through the cell membrane into the cells. MEE was intracellularly partly hydrolysed to GSH and caused a limited rise of intracellular GSH. DEE was intracellularly mainly converted into MEE and partly into GSH. DEE caused a larger rise of the intracellular GSH content than MEE; it also provided a better radioprotection. Radioprotection by the GSH esters may be explained by an increase of intracellular GSH as well as by the presence of the esters themselves. Cysteamine caused no rise of the intracellular GSH content, thus its radioprotection could not be mediated by an increase of intracellular GSH. When the radiosensitivity of GSH-depleted cells protected by cysteamine was compared with the radiosensitivity of non-GSH-depleted cells similarly protected by cysteamine, it appeared that the GSH-depleted cells remained more sensitive to irradiation. Thus, it seems that in this respect cysteamine cannot fully substitute for endogenous GSH.
Animals↗
Effects of BSO and DEM on thiol-level and radiosensitivity in HeLa cells.
Reduction of the intracellular GSH and NPSH levels in HeLa cells by BSO and DEM treatments was determined. The effect of a 16 to 22 hr incubation with BSO at 37 degrees C, resulting in a depletion of GSH and NPSH to about 10 and 50%, respectively, and the effect of a 50 min incubation with DEM resulting in a reduction of GSH and NPSH to about 30 and 60%, respectively, on radiation sensitivity were studied. As parameters for radiation damage, single and double strand DNA breaks (ssb and dsb) and cell killing were used. Furthermore, repair of ssb and dsb were followed in the first 30 to 120 min after radiation, respectively. BSO and DEM treatment gave a small sensitization for the 3 types of radiation damage (ssb, dsb and cell killing) in aerobic condition. In hypoxic condition the sensitizing effect of both compounds on dsb was larger than the effect on ssb. Pretreatment with BSO and DEM had no influence on repair of ssb and dsb when cells were irradiated in air, but when cells were irradiated in hypoxia, repair was somewhat inhibited after pretreatment with DEM. It can be postulated that a reduction of the intracellular GSH level by BSO and DEM treatment affects cellular radiosensitivity both by a competitive mechanism between GSH and O2 and by inhibition of enzymatic repair of DNA breaks, the latter only in the case of DEM treatment.
Buthionine Sulfoximine↗
Protection against X-irradiation by some orally administered compounds.
A number of compounds were studied that protected mice against LD50/30 after X-irradiation. For three compounds (WR 109342, WR 158490 and WR 159243) dose reduction factors between 1.7 and 1.8 were obtained after oral administration. Blood taken from mice that had been treated with these protective compounds provided virtually no protection of HeLa cells in vitro, whereas when blood from cysteamine treated mice was tested in vitro, protection could be demonstrated. This may indicate different mechanisms of action.
Adamantane↗