SELENIUM AND VITAMIN-E INHIBIT RADIOGENIC AND CHEMICALLY-INDUCED TRANSFORMATION INVITRO VIA DIFFERENT MECHANISMS

SELENIUM AND VITAMIN-E INHIBIT RADIOGENIC AND CHEMICALLY-INDUCED TRANSFORMATION INVITRO VIA DIFFERENT MECHANISMS
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DOI:
10.1073/pnas.83.5.1490
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发表时间:
1986-03-01
影响因子:
11.1
通讯作者:
BIAGLOW, JE
BIAGLOW, JE
中科院分区:
综合性期刊1区
文献类型:
--
作者:
BOREK, C;ONG, A;BIAGLOW, JE

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体内和体外研究结果表明,抗氧化剂可能作为抗癌剂支持活性氧在致癌作用中的作用,并提供了动力,探索膳食抗氧化剂在癌症预防中的功能,通过使用体外模型。我们研究了硒(谷胱甘肽过氧化物酶的一种成分)和维生素E(一种已知的抗氧化剂)对X射线、苯并[a]芘或色氨酸热解物诱导的C3 H/10 T-1/2细胞转化以及细胞清除系统和过氧化物破坏水平的单一和联合作用。C3 H/10 T-1/2细胞与2.5 μ M Na 2SeO 3(硒)或与7 μ M α-SeO 3(硒)孵育在暴露于X射线或化学致癌物之前24小时,维生素E琥珀酸酯导致每种抗氧化剂对转化的抑制,当两种营养素组合时具有相加-抑制作用。细胞预处理硒导致细胞谷胱甘肽过氧化物酶,过氧化氢酶,和非蛋白硫醇(谷胱甘肽)的水平增加,并在一个增强的破坏过氧化物。用维生素E预处理的细胞没有显示出这些生化作用,并且用维生素E和硒联合预处理没有增加硒对这些参数的影响。这些结果支持了我们早期的研究,表明自由基介导的事件在辐射和化学诱导的转化中发挥作用。他们指出,硒和维生素E单独或以相加的方式作为辐射防护剂和化学预防剂。结果进一步表明,硒赋予保护的一部分,诱导或激活细胞自由基清除系统,并通过增强过氧化物分解,而维生素E似乎赋予其保护的替代互补机制。
Results from in vivo and in vitro studies showing that antioxidants may act as anticarcinogens support the role of active oxygen in carcinogenesis and provide impetus for exploring the functions of dietary antioxidants in cancer prevention by using in vitro models. We examined the single and combined effects of selenium, a component of glutathione peroxidase, and vitamin E, a known antioxidant, on cell transformation induced in C3H/10T-1/2 cells by x-rays, benzo[a]pyrene, or tryptophan pyrolysate and on the levels of cellular scavenging systems and peroxide destruction. Incubation of C3H/10T-1/2 cells with 2.5 .mu.M Na2SeO3 (selenium) or with 7 .mu.M .alpha.-tocopherol succinate (vitamin E) 24 hr prior to exposure to x-rays or the chemical carcinogens resulted in an inhibition of transformation by each of the antioxidants with an additive-inhibitory action when the two nutrients were combined. Cellular pretreatment with selenium resulted in increased levels of cellular glutathione peroxidase, catalase, and nonprotein thiols (glutathione) and in an enhanced destruction of peroxide. Cells pretreated with vitamin E did not show these biochemical effects, and the combined pretreatment with vitamin E and selenium did not augment the effect of selenium on these parameters. The results support our earlier studies showing that free radical-mediated events play a role in radiation and chemically induced transformation. They indicate that selenium and vitamin E act alone and in additive fashion as radioprotecting and chemopreventing agents. The results further suggest that selenium confers protection in part by inducing or activating cellular free-radical scavenging systems and by enhancing peroxide breakdown while vitamin E appears to confer its protection by an alternate complementary mechanism.