首页> 外文期刊>Membrane and cell biology >Reduced cellular glutathione levels do not affect the cytotoxicity or photocytotoxicity of the cationic photosensitiser Victoria Blue BO.
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Reduced cellular glutathione levels do not affect the cytotoxicity or photocytotoxicity of the cationic photosensitiser Victoria Blue BO.

机译:降低的细胞谷胱甘肽水平不会影响阳离子光敏剂维多利亚蓝BO的细胞毒性或光细胞毒性。

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摘要

Victoria Blue BO (VBBO) is thought to exert its photocytotoxic effects via free radical generation. Glutathione and related enzymes are associated with the protection of normal tissues against free-radical damage and have also been implicated in multiple drug resistance. It might, therefore, be expected that cells containing higher levels of glutathione would be resistant to the cytotoxic effects of VBBO. The total glutathione content for a murine mammary tumour cell line, EMT6-S, was found to be lower than in a multi-drug resistant cell line, EMT6-R, 21.84+/-2.54 microg (mg protein)(-1) and 18.79+/-2.7 microg (mg protein)(-1), respectively; however, this was not found to be a significant difference (p > 0.05, Student t-test). Buthionine sulfoximine, a potent inhibitor of gamma-glutamyl cysteine synthetase, brought about a reduction in glutathione levels in both EMT6-S and EMT6-R cell lines in a concentration-dependent manner. Buthionine sulfoximine administration was effective in reducing intracellular glutathione levels by up to 90% in both types of cells. Interestingly, glutathione depletion of EMT6-S and EMT6-R cells did not enhance the photocytotoxic effect of VBBO, suggesting that the primary site of action of VBBO may be at an intracellular site not protected by glutathione or that the mechanism of action is not via the in situ generation of free radical species.
机译:维多利亚蓝BO(VBBO)被认为通过自由基产生发挥其光细胞毒性作用。谷胱甘肽和相关酶与保护正常组织免于自由基损伤有关,并且还涉及多种耐药性。因此,可以预期含有更高水平的谷胱甘肽的细胞将对VBBO的细胞毒性作用具有抗性。发现鼠类乳腺肿瘤细胞系EMT6-S的总谷胱甘肽含量低于多重耐药性细胞系EMT6-R的21.84 +/- 2.54 microg(mg蛋白)(-1)和分别为18.79 +/- 2.7 microg(mg蛋白)(-1);但是,这没有显着差异(p> 0.05,Student t检验)。丁硫氨酸亚砜亚胺,一种有效的γ-谷氨酰半胱氨酸合成酶抑制剂,以浓度依赖的方式降低了EMT6-S和EMT6-R细胞系中的谷胱甘肽水平。在两种类型的细胞中,丁基硫氨酸亚砜亚胺给药均可有效降低细胞内谷胱甘肽水平达90%。有趣的是,EMT6-S和EMT6-R细胞的谷胱甘肽耗竭并不能增强VBBO的光细胞毒性作用,这表明VBBO的主要作用位点可能位于不受谷胱甘肽保护的细胞内位点,或者作用机理并非通过自由基物种的原位生成。

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