Matsunaga K, Mashiba H
Division of Immunology, National Kyushu Cancer Center.
Gan To Kagaku Ryoho. 1990 Mar;17(3 Pt 2):452-8.
Roles of oxygen free radicals in recombinant human TNF- and human lymphotoxin (LT)-mediated cytotoxicity have been examined. Nimustine (ACNU), which inhibits glutathione reductase, and buthionine sulphoximine (BSO), an inhibitor of glutathione (GSH) synthesis, were used to modify the steady-state level of intracellular H2O2. TNF-mediated cytotoxicity was augmented when ACNU was added simultaneously to target L cells or Meth A tumor cells. Similar augmented effect was observed when TNF or LT was added to ACNU-treated target cells. However, the addition of GSH nullified the augmentation of TNF-mediated cytotoxicity to ACNU-treated Meth A tumor cells. Meth A tumor cells were pretreated with BSO for 24 hr, and thereafter TNF or LT was added in the presence or the absence of BSO. The cytotoxic effect of TNF and LT was augmented by the treatment of the cell with BSO or simultaneous addition of BSO. High degree of the augmentation was obtained when the pretreatment with BSO and further addition of BSO were combined. These results suggest that oxygen free radicals are closely involved in TNF- and LT-mediated cytotoxicity and the modulation of intracellular GSH level alters the degree of the cytotoxicity of these cytotoxins.
已对氧自由基在重组人肿瘤坏死因子（TNF）和人淋巴毒素（LT）介导的细胞毒性中的作用进行了研究。尼莫司汀（ACNU）可抑制谷胱甘肽还原酶，而丁硫氨酸亚砜胺（BSO）是谷胱甘肽（GSH）合成的抑制剂，二者被用于改变细胞内过氧化氢（H2O2）的稳态水平。当ACNU同时添加到靶细胞L细胞或Meth A肿瘤细胞中时，TNF介导的细胞毒性增强。当将TNF或LT添加到经ACNU处理的靶细胞中时，也观察到了类似的增强作用。然而，添加GSH可消除TNF介导的对经ACNU处理的Meth A肿瘤细胞的细胞毒性增强作用。将Meth A肿瘤细胞用BSO预处理24小时，然后在有或无BSO的情况下添加TNF或LT。用BSO处理细胞或同时添加BSO可增强TNF和LT的细胞毒性作用。当将BSO预处理与进一步添加BSO相结合时，可获得高度增强效果。这些结果表明，氧自由基与TNF和LT介导的细胞毒性密切相关，并且细胞内GSH水平的调节会改变这些细胞毒素的细胞毒性程度。
