GLUTATHIONE DEPLETION, RADIOSENSITIZATION, AND MISONIDAZOLE POTENTIATION IN HYPOXIC CHINESE-HAMSTER OVARY CELLS BY BUTHIONINE SULFOXIMINE
GLUTATHIONE DEPLETION, RADIOSENSITIZATION, AND MISONIDAZOLE POTENTIATION IN HYPOXIC CHINESE-HAMSTER OVARY CELLS BY BUTHIONINE SULFOXIMINE
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DOI：
10.2307/3576244
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发表时间：
1984-01-01
影响因子：
3.4
通讯作者：
ZACHGO, E
中科院分区：
文献类型：
--
作者：
CLARK, EP;EPP, ER;ZACHGO, E
丁硫酰亚胺（BSO）抑制谷胱甘肽（GSH）的合成，谷胱甘肽是大多数哺乳动物细胞中存在的主要非蛋白巯基（NPSH）。1 μ M至0.1 mM的BSO浓缩物以不同的速率降低细胞内GSH，而BSO ≥ 0.1 mM。0.1 mM（即，0.1-2.0 mM），导致抑制剂酶饱和，在10 h内以大约相等的速率将GSH耗尽至对照的< 10%。在这些实验中使用的BSO暴露没有细胞毒性，除了2.0mM BSO/24小时将细胞活力降低至约百分之五十然而，用于确定其放射增敏作用的BSO暴露未观察到细胞倍增时间或细胞年龄密度分布的改变。当GSH和NPSH浓度分别降低至<对照的10%和20%时，BSO显著地放射增敏（ER = 1.41，0.1mM BSO/24小时）缺氧但不需氧的CHO细胞，并且甚至用μ M浓度的BSO（ER = 1.38，10 μ M BSO/2小时）达到最大放射增敏性。此外，BSO暴露（0.1 mM BSO/24 h）也增强了不同浓度的米索硝唑对缺氧CHO细胞的放射增敏作用。
Buthionine sulfoximine (BSO) inhibits the synthesis of glutathione (GSH), the major nonprotein sulfhydryl (NPSH) present in most mammalian cells. BSO concentrates from 1 .mu.M to 0.1 mM reduced intracelullar GSH at different rates, while BSO .gtoreq. 0.1 mM (i.e., 0.1-2.0 mM), resulting in inhibitor enzyme saturation, depleted GSH to < 10% of control within 10 h at about equal rates. BSO exposures used in these experiments were not cytotoxic with the-one exception that 2.0 mM BSO/24 h reduced cell viability to .apprx. 50%. However, alterations in either the cell doubling time(s) or the cell age density distribution(s) were not observed with the BSO exposures used to determine its radiosensitizing effect. BSO significantly radiosensitized (ER = 1.41 with 0.1 mM BSO/24 h) hypoxic, but not aerobic, CHO cells when the GSH and NPSH concentrations were reduced to < 10 and 20% of control, respectively, and maximum radiosensitivity was even achieved with .mu.M concentrations of BSO (ER = 1.38 with 10 .mu.M BSO/2 h). Furthermore, BSO exposure (0.1 mM BSO/24 h) also enhanced the radiosensitizing effect of various concentrations of misonidazole on hypoxic CHO cells.