Decreased ratio of reduced/oxidized glutathione in mouse epidermal cells treated with tumor promoters.
Decreased ratio of reduced/oxidized glutathione in mouse epidermal cells treated with tumor promoters.
复制标题
用肿瘤促进剂处理的小鼠表皮细胞中还原型/氧化型谷胱甘肽的比例降低。
DOI：
10.1093/carcin/7.3.503
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发表时间：
1986
期刊：
影响因子：
4.7
通讯作者：
B. Schneider
中科院分区：
文献类型：
--
作者：
J. Perchellet;E. Perchellet;D. K. Orten;B. Schneider
细胞促氧化状态似乎在促进阶段发挥作用，可能是因为肿瘤促进剂处理的细胞过度产生活化形式的氧和/或缺乏破坏它们的能力。由于对强效肿瘤启动子12- o -十四烷醇-13-乙酸酯（TPA）最早的反应之一可能是产生活性氧，我们已经确定了该化合物对天然谷胱甘肽依赖的表皮细胞抗氧化保护系统的影响。在这里，我们报道了八种（化学上不同的）肿瘤促进剂（包括磷酯、过氧化氢、过氧化苯甲酰、蒽醌和mezerein）不同程度地降低小鼠表皮细胞内还原性(GSH)/氧化性（GSSG）谷胱甘肽的细胞内比率。TPA导致GSH过氧化物酶活性在20分钟内迅速、短暂地增加，同时GSH/GSSG比值显著降低。1 h后，虽然GSH/GSSG的比值仍然很低，但在tpa处理的表皮细胞中，GSH过氧化物酶活性下降到对照水平以下。这一序列表明，细胞中依赖gsh的解毒系统最初是开启的，但随后迅速被与TPA促肿瘤活性相关的氧化挑战所淹没。由于自由基清除剂、GSH升高剂和含硒化合物均抑制TPA对GSH代谢和促进肿瘤的作用，因此我们提出TPA治疗过程中对表皮细胞GSH依赖性抗氧化保护系统的增强可能抑制皮肤肿瘤的促进。
Cellular pro-oxidant states appear to play role in the promotion phase, presumably because tumor promoter-treated cells overproduce activated forms of oxygen and/or deficient in their ability to destroy them. Since one of the earliest responses to the potent tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA) may be the generation of reactive oxygen species, we have determined the effects of this compound on the natural glutathione-dependent antioxidant protective system of the epidermal cells. Here we report that eight (chemically different) tumor promoters (including the phorbol esters, hydrogen peroxide, benzoyl peroxide, anthralin and mezerein) decreases to various degrees the intracellular ratio of reduced (GSH)/oxidized (GSSG) glutathione in isolated mouse epidermal cells. TPA leads to a rapid, transient increase in GSH peroxidase activity within 20 min, concomitant with a marked decrease in the ratio of GSH/GSSG. Beyond 1 h, while the GSH/GSSG ratio remains low, the GSH peroxidase activity declines below the control level in TPA-treated epidermal cells. This sequence suggests that the GSH-dependent detoxifying system of the cell is initially turned on but then rapidly overwhelmed by the oxidative challenge linked to the tumor-promoting activity of TPA. Since free radical scavengers, GSH level-raising agents and selenium-containing compounds all inhibit the effects of TPA on both GSH metabolism and tumor promotion, it is proposed that the enhancement of the GSH-dependent antioxidant protective system of the epidermal cells during TPA treatment might inhibit skin tumor promotion.