Miller A C, Henderson B W
Radiat Res. 1986 Jul;107(1):83-94.
The influence of cellular glutathione (GSH) levels on the response to photodynamic treatment (PDT) in vitro was determined in cells which either were depleted of GSH by buthionine sulfoximine (BSO) or were genetically GSH deficient. The effects of GSH depletion on cellular radiosensitivity were studied in parallel for the purpose of comparison. BSO treatments which reduced GSH levels in four cell lines (CHO, V79, EMT6, RIF) to approximately 80% of controls, 30% of controls, or undetectable levels uniformly decreased cell survival. This decrease was directly related to GSH depletion levels and was expressed mainly in a reduction of the width of the survival curve shoulder (Dq). GSH level-dependent aerobic radiosensitization following BSO treatment was likewise found in all four cell lines. In contrast to PDT, however, cell survival changes were expressed in the dose slopes (Do's) of the survival curves. Cell survival of GSH-deficient human fibroblasts (GM 3877) was decreased following PDT and gamma irradiation when compared to their normal counterparts (GM 5659). In both modalities the difference was mainly due to a reduction in the Dq's, while the Do's were only slightly affected. The augmented response to PDT was not caused by interference by BSO or GSH with either cellular porphyrin uptake or singlet oxygen production during the photodynamic process. Possible mechanisms of GSH effects on PDT were discussed.
在通过丁硫氨酸亚砜胺（BSO）使谷胱甘肽（GSH）耗竭的细胞或遗传性GSH缺陷的细胞中，测定了细胞内GSH水平对体外光动力治疗（PDT）反应的影响。为作比较，同时研究了GSH耗竭对细胞放射敏感性的影响。BSO处理使四种细胞系（CHO、V79、EMT6、RIF）中的GSH水平分别降至对照水平的约80%、30%或检测不到的水平，均一致降低了细胞存活率。这种降低与GSH耗竭水平直接相关，主要表现为存活曲线肩部宽度（Dq）减小。在所有四种细胞系中同样发现了BSO处理后GSH水平依赖性的需氧放射增敏作用。然而，与PDT不同的是，细胞存活变化表现在存活曲线的剂量斜率（Do）上。与正常的人成纤维细胞（GM 5659）相比，GSH缺陷的人成纤维细胞（GM 3877）在PDT和γ射线照射后的细胞存活率降低。在这两种模式下，差异主要是由于Dq减小，而Do仅受到轻微影响。对PDT增强的反应不是由BSO或GSH在光动力过程中干扰细胞卟啉摄取或单线态氧产生所致。讨论了GSH对PDT作用的可能机制。
