THE ROLE OF GLUTATHIONE IN THE AEROBIC RADIORESPONSE .1. SENSITIZATION AND RECOVERY IN THE ABSENCE OF INTRACELLULAR GLUTATHIONE
THE ROLE OF GLUTATHIONE IN THE AEROBIC RADIORESPONSE .1. SENSITIZATION AND RECOVERY IN THE ABSENCE OF INTRACELLULAR GLUTATHIONE
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DOI：
10.2307/3576912
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发表时间：
1986-12-01
影响因子：
3.4
通讯作者：
BIAGLOW, JE
中科院分区：
文献类型：
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作者：
CLARK, EP;EPP, ER;BIAGLOW, JE
在CHO-10B4、V79和A549三个细胞系中研究了细胞内谷胱甘肽（GSH）浓度和细胞外还原等价物浓度的变化对有氧放射致敏的影响。在丁硫氨酸亚砜（BSO）抑制谷胱甘肽合成后，细胞内谷胱甘肽被代谢耗尽，而细胞外环境则通过用无硫醇盐溶液替代生长培养基，在一些实验中通过外源添加谷胱甘肽或GSSG来控制。当细胞内GSH被广泛消耗（1.0 mM BSO/24小时处理后GSH < 1 nmol GSH/106个细胞），细胞外环境的复杂性降低时，所检测的每个细胞系都表现出增强的有氧辐射反应。虽然在辐照前向细胞中添加氧化谷胱甘肽（5 mM GSH/ 30分钟）没有效果，但添加还原性谷胱甘肽（5 mM GSH/15分钟）可以克服大部分或所有诱导的放射敏感性。然而，观察到外源GSH添加恢复对照辐射响应而不增加细胞内GSH浓度是完全出乎意料的。这些结果表明，许多因素对谷胱甘肽消耗的程度产生影响，并决定有氧放射致敏的程度。此外，外源性谷胱甘肽与细胞膜的相互作用（但不穿透细胞膜）足以导致放射性恢复。
The effect of changes in both the intracellular glutathione (GSH) concentration and the concentration of extracellular reducing equivalents on the aerobic radiosensitization was studied in three cell lines: CHO-10B4, V79, and A549. Intracellular GSH was metabolically depleted after the inhibition of GSH synthesis by buthionine sulfoximine (BSO), while the extracellular environment was controlled through the replacement of growth medium with a thiol-free salt solution and in some experiments by the exogenous addition of either GSH or GSSG. Each of the cell lines examined exhibited an enhanced aerobic radioresponse when the intracellular GSH was extensively depleted (GSH < 1 nmol GSH/106 cells after 1.0 mM BSO/24 h treatment) and the complexity of the extracellular milieu decreased. Although the addition of oxidized glutathione (5 mM GSSG/30 min) to cells prior to irradiation was without effect, much orall of the induced radiosensitivity was overcome by the addition of reduced glutathione (5 mM GSH/15 min). However, the observation that the exogenous GSH addition restores the control radioresponse without increasing the intracellular GSH concentration was entirely unexpected. These results suggest that a number of factors exert an influence on the extent of GSH depletion and determine the extent of aerobic radiosensitization. Furthermore, the interaction of exogenous GSH with-but without penetrating-the cell membrane is sufficient to result in radiorecovery.