van der Schans G P, Vos O, Roos-Verheij W S, Lohman P H
Int J Radiat Biol Relat Stud Phys Chem Med. 1986 Sep;50(3):453-70. doi: 10.1080/09553008614550861.
Treatment of mammalian cells with buthionine sulphoximine (BSO) or diethyl maleate (DEM) results in a decrease in the intracellular GSH (glutathione) and non-protein-bound SH (NPSH) levels. The effect of depletion of GSH and NPSH on radiosensitivity was studied in relation to the concentration of oxygen during irradiation. Single- and double-strand breaks (ssb and dsb) and cell killing were used as criteria for radiation damage. Under aerobic conditions, BSO and DEM treatment gave a small sensitization of 10-20 per cent for the three types of radiation damage. Also under severely hypoxic conditions (0.01 microM oxygen in the medium) the sensitizing effect of both compounds on the induction of ssb and dsb and on cell killing was small (0-30 per cent). At somewhat higher concentrations of oxygen (0.5-10 microM) however, the sensitization amounted to about 90 per cent for the induction of ssb and dsb and about 50 per cent for cell killing. These results strengthen the widely accepted idea that intracellular SH-compounds compete with oxygen and other electron-affinic radiosensitizers with respect to reaction with radiation-induced damage, thus preventing the fixation of DNA damages by oxygen. These results imply that the extent to which SH-compounds affect the radiosensitivity of cells in vivo depends strongly on the local concentration of oxygen.
用丁硫氨酸亚砜胺（BSO）或马来酸二乙酯（DEM）处理哺乳动物细胞会导致细胞内谷胱甘肽（GSH）和非蛋白结合巯基（NPSH）水平降低。研究了GSH和NPSH耗竭对放射敏感性的影响，并与辐照期间的氧浓度相关。单链和双链断裂（ssb和dsb）以及细胞杀伤被用作辐射损伤的标准。在有氧条件下，BSO和DEM处理对三种类型的辐射损伤产生了10%-20%的小幅度增敏作用。同样在严重缺氧条件下（培养基中氧浓度为0.01微摩尔），这两种化合物对ssb和dsb诱导以及细胞杀伤的增敏作用较小（0%-30%）。然而，在氧浓度稍高时（0.5-10微摩尔），ssb和dsb诱导的增敏作用达到约90%，细胞杀伤的增敏作用达到约50%。这些结果强化了一个被广泛接受的观点，即细胞内的巯基化合物在与辐射诱导损伤反应方面与氧和其他亲电子放射增敏剂竞争，从而阻止氧对DNA损伤的固定。这些结果表明，巯基化合物在体内影响细胞放射敏感性的程度强烈依赖于局部氧浓度。
