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.
D019328:Buthionine Sulfoximine; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004260:DNA Repair; D004273:DNA, Neoplasm / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D006367:HeLa Cells / Q000378:metabolism*; D006801:Humans; D008298:Maleates / Q000494:pharmacology*; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D013438:Sulfhydryl Compounds / Q000378:metabolism*
D004273:DNA, Neoplasm; D008298:Maleates; D011838:Radiation-Sensitizing Agents; D013438:Sulfhydryl Compounds; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; C014476:diethyl maleate