RESISTANCE OF HUMAN-TUMOR CELLS-INVITRO TO OXIDATIVE CYTOLYSIS
RESISTANCE OF HUMAN-TUMOR CELLS-INVITRO TO OXIDATIVE CYTOLYSIS
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DOI：
10.1172/jci111981
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发表时间：
1985-01-01
影响因子：
15.9
通讯作者：
NATHAN, CF
中科院分区：
文献类型：
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作者：
ODONNELLTORMEY, J;DEBOER, CJ;NATHAN, CF
9种人类细胞类型，其中6种是恶性细胞，对过氧化氢裂解显示出显著的抗性（LD 50 [50%致死剂量]，2-20 mM）。在细胞外产生的活性O2中间产物中，只有H2 O2溶解所有细胞类型。OH对四种细胞类型中的一种细胞溶解，OI对一种细胞溶解，O2对4种细胞类型中的任何一种细胞都不溶解。抗氧化裂解与过氧化氢酶，谷胱甘肽（GSH）过氧化物酶，其他过氧化物酶，谷胱甘肽二硫还原酶，或与特定的GSH含量的比活性不相关。对H2 O2的抗性似乎是通过与细胞消耗H2 O2不同的机制发生的。消耗是可重复的叠氮化物，可能是由于过氧化氢酶在每种细胞类型。对氧化裂解的抗性通过不同的途径在不同的细胞中发生。一种细胞类型使用GSH氧化还原循环作为对H2 O2的主要防御，如先前研究的小鼠肿瘤。其他细胞似乎利用过氧化氢酶作为对H2 O2的主要防御。随着过氧化氢酶和GSH氧化还原循环的抑制，所有测试的人类细胞都表现出对氧化裂解的固有抗性，即抗性独立于H2 O2的可检测降解。
Nine human cell types, 6 of them malignant, displayed a marked resistance to lysis by hydrogen peroxide (LD50 [50% lethal dose], 2-20 mM). Of the reactive O2 intermediates generated extracellularly, only H2O2 lysed all the cell types. OH was lytic to one of four, OI- to one of one, and O2- to none of 4 cell types tested. Resistance to oxidative lysis did not correlate with specific activity of catalase, glutathione (GSH) peroxidase, other peroxidases, or glutathione disulfide reductase, or with specific content of GSH. Resistance to H2O2 seemed to occur via mechanisms distinct from those responsible for cellular consumption of H2O2. Consumption was inhibitable by azide and was probably due to catalase in each cell type. Resistance to oxidative lysis occurred via distinct routes in different cells. One cell type used the GSH redox cycle as the primary defense against H2O2, like murine tumors previously studied. Other cells seemed to utilize catalase as the major defense against H2O2. With both catalase and the GSH redox cycle inhibited, all the human cells tested exhibited an inherent resistance to oxidative lysis, that is, resistance independent of detectable degradation of H2O2.