Koch C J, Stobbe C C, Baer K A
Int J Radiat Oncol Biol Phys. 1986 Jul;12(7):1151-5. doi: 10.1016/0360-3016(86)90247-6.
Radiosensitization of V79 Chinese hamster fibroblasts by 0.5 mM misonidazole is a smooth function of endogenous glutathione (GSH) levels as modulated upwards by pre-incubation in medium containing cysteamine, or downwards by pre-incubation in medium containing buthionine sulfoximine. The enhancement ratio (radiation sensitivity in nitrogen/radiation sensitivity in nitrogen +/- sensitizer or thiol) varies from 1.3 at 12 mM to 2.25 at less than 0.1 mM endogenous GSH. The enhanced radiosensitivity of thiol-depleted hypoxic cells is reversed when exogenous thiols are added, and for equivalent ER, the exogenous thiol concentrations are much lower than the endogenous GSH concentrations. Measurement of intracellular drug concentrations amplified rather than diminished the above discrepancy, since intracellular concentrations of cysteamine were lower and glutathione much lower than the extracellular concentrations. Three possible explanations are addressed: an external membrane component of damage is involved, long-range protection to DNA target radicals is possible from outside the cell (e.g., donation of electrons), and (c) endogenous glutathione is not in a free or exchangeable state (e.g., bound).
0.5 mM 米索硝唑对 V79 中国仓鼠成纤维细胞的放射增敏作用是内源性谷胱甘肽（GSH）水平的平滑函数，通过在含半胱胺的培养基中预孵育可上调 GSH 水平，而在含丁硫氨酸亚砜胺的培养基中预孵育则可下调 GSH 水平。增强比（氮气中的辐射敏感性/氮气中加或不加增敏剂或硫醇时的辐射敏感性）在内源性 GSH 为 12 mM 时为 1.3，在内源性 GSH 小于 0.1 mM 时为 2.25。当添加外源性硫醇时，硫醇耗竭的缺氧细胞增强的放射敏感性会逆转，并且对于等效的增强比，外源性硫醇浓度远低于内源性 GSH 浓度。细胞内药物浓度的测量放大而非减小了上述差异，因为细胞内半胱胺浓度较低，而谷胱甘肽浓度远低于细胞外浓度。文中探讨了三种可能的解释：涉及损伤的外膜成分、从细胞外部可能对 DNA 靶自由基进行远程保护（例如电子供体），以及（c）内源性谷胱甘肽不是处于游离或可交换状态（例如结合状态）。
