Mitchell J B, Russo A, Biaglow J E, McPherson S
Radiat Res. 1983 Nov;96(2):422-8.
The hypoxic and euoxic radiation response for Chinese hamster lung and A549 human lung carcinoma cells was obtained under conditions where their nonprotein thiols, consisting primarily of glutathione (GSH), were depleted by different mechanisms. The GSH conjugating reagent diethylmaleate (DEM) was compared to DL-buthionine-S,R-sulfoximine (BSO), an inhibitor of glutathionine biosynthesis. Each reagent depleted cellular GSH to less than 5% of control values. A 2-hr exposure to 0.5 mM DEM or a 4- or 24-hr exposure to BSO at 10 or 1 mM, respectively, depleted cellular GSH to less than 5% of control values. Both agents sensitized cells irradiated under air or hypoxic conditions. When GSH levels are lowered to less than 5% by both agents, hypoxic DEM-treated cells exhibited slightly greater X-ray sensitization than hypoxic BSO-treated cells. The D0's for hypoxic survival curves were as follows: control, 4.87 Gy; DEM, 3.22 Gy; and BSO, 4.30 Gy for the V79 cells and 5.00 Gy versus 4.02 Gy for BSO-treated A549 cells. The D0's for aerobic V79 cells were 1.70 Gy versus 1.13 Gy, DEM, and 1.43 Gy for BSO-treated cells. The D0's for the aerobic A549 were 1.70 and 1.20 for BSO-treated cells. The aerobic and anoxic sensitization of the cells results in the OER's of 2.8 and 3.0 for the DEM- and BSO-treated cells compared to 2.9 for the V79 control A549. BSO-treated cells showed an OER of 3.3 versus 3 for the control. Our results suggest that GSH depletion by either BSO or DEM sensitizes aerobic cells to radiation but does not appreciably alter the OER.
在中国仓鼠肺细胞和A549人肺癌细胞中，通过不同机制耗尽其主要由谷胱甘肽（GSH）组成的非蛋白质硫醇后，获得了缺氧和常氧辐射反应。将谷胱甘肽结合试剂马来酸二乙酯（DEM）与谷胱甘肽生物合成抑制剂DL-丁硫氨酸-S，R-亚砜亚胺（BSO）进行了比较。每种试剂都将细胞内谷胱甘肽耗尽至对照值的5%以下。分别用0.5 mM DEM处理2小时或用10或1 mM BSO处理4或24小时，可将细胞内谷胱甘肽耗尽至对照值的5%以下。两种试剂均使在空气或缺氧条件下照射的细胞致敏。当两种试剂都将谷胱甘肽水平降低到5%以下时，缺氧DEM处理的细胞比缺氧BSO处理的细胞表现出稍大的X射线致敏性。缺氧存活曲线的D0值如下：V79细胞对照组为4.87 Gy，DEM组为3.22 Gy，BSO组为4.30 Gy；A549细胞对照组为5.00 Gy versus BSO处理组为4.02 Gy。有氧V79细胞的D0值对照组为1.70 Gy，DEM组为1.13 Gy，BSO处理组为1.43 Gy。有氧A549细胞的D0值BSO处理组为1.70和1.20。与V79对照A549细胞的2.9相比，DEM和BSO处理细胞的有氧和缺氧致敏导致OER分别为2.8和3.0。BSO处理细胞的OER为3.3，而对照组为3.0。我们的结果表明，BSO或DEM耗尽谷胱甘肽会使有氧细胞对辐射致敏，但不会明显改变OER。
