Vos O, van der Schans G P, Roos-Verhey W S
Int J Radiat Oncol Biol Phys. 1984 Aug;10(8):1249-53. doi: 10.1016/0360-3016(84)90327-4.
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.
测定了用丁硫氨酸亚砜胺（BSO）和二乙马来酸酐（DEM）处理对HeLa细胞内谷胱甘肽（GSH）和非蛋白巯基（NPSH）水平的降低情况。研究了在37℃下用BSO孵育16至22小时，导致GSH和NPSH分别耗竭至约10%和50%的效果，以及用DEM孵育50分钟，导致GSH和NPSH分别降低至约30%和60%对辐射敏感性的影响。作为辐射损伤的参数，使用了单链和双链DNA断裂（ssb和dsb）以及细胞杀伤情况。此外，分别在辐射后的前30至120分钟跟踪了ssb和dsb的修复情况。在有氧条件下，BSO和DEM处理对3种辐射损伤（ssb、dsb和细胞杀伤）产生了较小的增敏作用。在缺氧条件下，这两种化合物对dsb的增敏作用大于对ssb的作用。当细胞在空气中照射时，用BSO和DEM预处理对ssb和dsb的修复没有影响，但当细胞在缺氧条件下照射时，用DEM预处理后修复受到一定抑制。可以推测，通过BSO和DEM处理降低细胞内GSH水平，通过GSH与O2之间的竞争机制以及抑制DNA断裂的酶促修复来影响细胞放射敏感性，后者仅在DEM处理的情况下发生。
