Henderson B W, Miller A C
Radiat Res. 1986 Nov;108(2):196-205.
The effects of various scavengers of reactive oxygen and/or radical species on cell survival in vitro of EMT6 and CHO cells following photodynamic therapy (PDT) or gamma irradiation were compared. None of the agents used exhibited major direct cytotoxicity. Likewise, none interfered with cellular porphyrin uptake, and none except tryptophan altered singlet oxygen production during porphyrin illumination. The radioprotector cysteamine (MEA) was equally effective in reducing cell damage in both modalities. In part, this protection seems to have been induced by oxygen consumption in the system due to MEA autoxidation under formation of H2O2. The addition of catalase, which prevents H2O2 buildup, reduced the effect of MEA to the same extent in both treatments. Whether the remaining protection was due to MEA's radical-reducing action or some remaining oxygen limitation is unclear. The protective action of MEA was not mediated by a doubling of cellular glutathione levels, since addition of buthionine sulfoximine, which prevented glutathione increase, did not diminish the observed MEA protection. The hydroxyl radical scavenger mannitol also afforded protection in both kinds of treatment, but it was approximately twice as effective in gamma irradiation as in PDT. This is consistent with the predominant role of OH radicals in ionizing radiation damage and their presumed minor involvement in PDT damage. Superoxide dismutase, a scavenger of O2, acted as a radiation protector but was not significantly effective in PDT. Catalase, which scavenges H2O2, was ineffective in both modalities. Tryptophan, an efficient singlet oxygen scavenger, reduced cell death through PDT by several orders of magnitude while being totally ineffective in gamma irradiation. These data reaffirm the predominant role of 1O2 in the photodynamic cell killing but also indicate some involvement of free radical species.
比较了各种活性氧和/或自由基清除剂对光动力疗法（PDT）或γ射线照射后EMT6和CHO细胞体外存活的影响。所使用的试剂均未表现出主要的直接细胞毒性。同样，没有一种试剂干扰细胞卟啉摄取，除色氨酸外，没有一种试剂改变卟啉光照期间单线态氧的产生。辐射防护剂半胱胺（MEA）在两种模式下减少细胞损伤方面同样有效。部分而言，这种保护似乎是由于MEA在形成H2O2的情况下自动氧化导致系统中耗氧所诱导的。添加过氧化氢酶可防止H2O2积累，在两种处理中均将MEA的作用降低到相同程度。尚不清楚其余的保护作用是由于MEA的自由基还原作用还是一些剩余的氧限制。MEA的保护作用不是由细胞谷胱甘肽水平加倍介导的，因为添加丁硫氨酸亚砜胺可防止谷胱甘肽增加，但并未减弱观察到的MEA保护作用。羟基自由基清除剂甘露醇在两种处理中也都提供了保护，但在γ射线照射中的效果约为PDT中的两倍。这与OH自由基在电离辐射损伤中的主要作用及其在PDT损伤中可能的次要作用一致。超氧化物歧化酶（一种O2清除剂）作为辐射防护剂，但在PDT中效果不显著。清除H2O2的过氧化氢酶在两种模式下均无效。色氨酸是一种有效的单线态氧清除剂，通过PDT使细胞死亡降低了几个数量级，而在γ射线照射中则完全无效。这些数据再次证实了1O2在光动力细胞杀伤中的主要作用，但也表明自由基物种有一定参与。
